Abstract
Patients with congenital aortic valve stenosis (AVS) can remain asymptomatic but may develop progressive and often underestimated exercise intolerance. The risk of increased left ventricular (LV) wall stress, irreversible myocardial fibrosis and sudden death in untreated patients warrants earlier intervention. The timing for curative therapy for severe AVS is clear, but optimal timing for moderate stenosis (modAS) is unknown. AVS often coexists with aortic regurgitation, which adds a volume overload to an already pressure-overloaded LV, adding an additional challenge to the estimation of disease severity. We investigated the possible value of N-terminal pro-brain natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hs-cTnT) upon treadmill exercise challenge in children with asymptomatic modAS versus moderate regurgitation (modAR). The aim was to determine optimal timing of peak biochemical response. Blood samples were obtained at rest, and then at 20, 40 and 60 min after peak exercise comparing modAS and modAR to healthy controls. Exercise performance was equivalent in all groups, with no difference for biomarker levels at rest. The increase in NT-proBNP was significant in modAR at 40 min (99.2 ± 48.6 ng/L; p = 0.04) and 60 min into recovery (100.0 ± 53.7 ng/L; p = 0.01), but not in modAS. The increase in hs-cTnT was significant only at 60 min into recovery for modAS and modAR. NT-proBNP and hs-cTnT following exercise challenge are possible discriminant biomarkers of modAR from modAS and controls at 60 min into recovery despite comparable exercise performance. This offers a promising avenue for future stratification of aortic valve disease and optimal timing of intervention.
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Azevedo CF, Nigri M, Higuchi ML et al (2010) Prognostic significance of myocardial fibrosis quantification by histopathology and magnetic resonance imaging in patients with severe aortic valve disease. J Am Coll Cardiol 56:278–287. doi:10.1016/j.jacc.2009.12.074
Bergler-Klein J, Gyöngyösi M, Maurer G (2014) The role of biomarkers in valvular heart disease: focus on natriuretic peptides. Can J Cardiol 30:1027–1034. doi:10.1016/j.cjca.2014.07.014
Beroukhim RS, Graham DA, Margossian R et al (2010) An echocardiographic model predicting severity of aortic regurgitation in congenital heart disease. Circ Cardiovasc Imaging 3:542–549. doi:10.1161/CIRCIMAGING.110.957175
Bonow RO, Carabello BA, Chatterjee K et al (2006) ACC/AHA 2006 practice guidelines for the management of patients with valvular heart disease: executive summary. J Am Coll Cardiol 48:598–675. doi:10.1016/j.jacc.2006.05.030
Capoulade R, Magne J, Dulgheru R et al (2014) Prognostic value of plasma B-type natriuretic peptide levels after exercise in patients with severe asymptomatic aortic stenosis. Heart 100:1606–1612. doi:10.1136/heartjnl-2014-305729
Collinson PO, Barnes SC, Gaze DC, Galasko G, Lahiri A, Senior R (2004) Analytical performance of the N terminal pro B type natriuretic peptide (NT-proBNP) assay on the Elecsys 1010 and 2010 analysers. Eur J Heart Fail 6:365–368
Dahdah N, Siles A, Fournier A et al (2009) Natriuretic peptide as an adjunctive diagnostic test in the acute phase of Kawasaki disease. Pediatr Cardiol 30:810–817
de Lemos JA, McGuire DK, Drazner MH (2003) B-type natriuretic peptide in cardiovascular disease. Lancet 362:316–322. doi:10.1016/S0140-6736(03)13976-1
Lindahl B, Venge P, James S (2010) The new high-sensitivity cardiac troponin T assay improves risk assessment in acute coronary syndromes. Am Heart J 160:224–229
Lopez L, Colan SD, Frommelt PC, Ensing GJ, Kendall K, Younoszai AK et al (2010) Recommendations for quantification methods during the performance of a pediatric echocardiogram: a report from the Pediatric Measurements Writing Group of the American Society of Echocardiography Pediatric and Congenital Heart Disease Council. J Am Soc Echocardiogr 23:465–495
Maeda K, Tsutamoto T, Wada A, Hisanaga T, Kinoshita M (1998) Plasma brain natriuretic peptide as a biochemical marker of high left ventricular end-diastolic pressure in patients with symptomatic left ventricular dysfunction. Am Heart J 135:825–832
Marcus KA, Mavinkurve-Groothuis AMC, Barends M et al (2011) Reference values for myocardial two-dimensional strain echocardiography in a healthy pediatric and young adult cohort. J Am Soc Echocardiogr 24:625–636. doi:10.1016/j.echo.2011.01.021
Mir TS, Haddad M, Laer S (2006) N-Terminal pro-brain natriuretic peptide: normal ranges in the pediatric population including method comparison and interlaboratory variability. Clin Chem Lab Med 44:80–85
Mischie AN, Andrei CL, Sinescu C (2013) Viewpoint: the ENIGMAS trial—When should we treat patients with moderate aortic stenosis? Echocardiography 30:599–615. doi:10.1111/echo.12080
Monin J-L, Lancellotti P, Monchi M et al (2009) Risk score for predicting outcome in patients with asymptomatic aortic stenosis. Circulation 120:69–75. doi:10.1161/CIRCULATIONAHA.108.808857
Nakagawa O, Ogawa Y, Itoh H et al (1995) Rapid transcriptional activation and early mRNA turnover of brain natriuretic peptide in cardiocyte hypertrophy. Evidence for brain natriuretic peptide as an “emergency” cardiac hormone against ventricular overload. J Clin Invest 96:1280–1287
Nishimura RA, Otto CM, Bonow RO et al (2014) 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 63:e57–e185. doi:10.1016/j.jacc.2014.02.536
Otto CM (2004) Aortic stenosis: even mild disease is significant. Eur Heart J 25:185–187
Otto CM, Burwash IG, Legget ME et al (1997) Prospective study of asymptomatic valvular aortic stenosis. Clinical, echocardiographic, and exercise predictors of outcome. Circulation 95:2262–2270
Pellikka PA, Sarano ME, Nishimura RA et al (2005) Outcome of 622 adults with asymptomatic, hemodynamically significant aortic stenosis during prolonged follow-up. Circulation 111:3290–3295. doi:10.1161/CIRCULATIONAHA.104.495903
Pizarro R, Bazzino OO, Oberti PF et al (2011) Prospective validation of the prognostic usefulness of B-type natriuretic peptide in asymptomatic patients with chronic severe aortic regurgitation. J Am Coll Cardiol 58:1705–1714. doi:10.1016/j.jacc.2011.07.016
Røsjø H, Andreassen J, Edvardsen T, Omland T (2011) Prognostic usefulness of circulating high-sensitivity Troponin T in aortic stenosis and relation to echocardiographic indexes of cardiac function and anatomy. Am J Cardiol 108:88–91
Saunders JT, Nambi V, de Lemos JA et al (2011) Cardiac troponin T measured by a highly sensitive assay predicts coronary heart disease, heart failure, and mortality in the Atherosclerosis Risk in Communities Study. Circulation 123:1367–1376
Scherr J, Braun S, Schuster T, Hartmann C et al (2011) 72-h kinetics of high-sensitive troponin T and inflammatory markers after marathon. Med Sci Sports Exerc 43:1819–1827
Vanderheyden M, Bartunek J, Goethals M (2004) Brain and other natriuretic peptides: molecular aspects. Eur J Heart Fail 6:261–268
Weidemann F, Herrmann S, Störk S et al (2009) Impact of myocardial fibrosis in patients with symptomatic severe aortic stenosis. Circulation 120:577–584. doi:10.1161/CIRCULATIONAHA.108.847772
Witthaut R (2004) Science review: natriuretic peptides in critical illness. Crit Care 8:342–349
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For this Investigator Initiated Proposal, received partial funding, monetary and in kind, from Roche Diagnostics, Switzerland.
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Mawad, W., Abadir, S., Fournier, A. et al. Timing of Dynamic NT-proBNP and hs-cTnT Response to Exercise Challenge in Asymptomatic Children with Moderate Aortic Valve Regurgitation or Moderate Aortic Valve Stenosis. Pediatr Cardiol 36, 1735–1741 (2015). https://doi.org/10.1007/s00246-015-1225-2
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DOI: https://doi.org/10.1007/s00246-015-1225-2