Abstract
Aortic valve stenosis is the commonest form of valvular heart disease in the Western world, currently affecting about 7% of the population over the age of 60, while 3% of people over the age of 75 have severe stenosis. With an aging population, its prevalence is expected to increase dramatically in the next few decades with major financial implications for global healthcare systems. Aortic stenosis is characterized by progressive valve narrowing that leads to a high-pressure load on the left ventricle (LV), triggering hypertrophy of cardiac myocytes, and increase in LV wall thickness and mass.
At present there is no effective medical therapy capable of altering disease progression so that the only treatment is aortic valve replacement (AVR), usually with either surgical or percutaneous techniques. Current international guidelines recommended AVR in patients with severe stenosis and evidence of LV decompensation (either on the basis of symptoms or a reduced ejection fraction). Following AVR patients demonstrate a variable degree of regression of the ventricular hypertrophy with favorable prognosis demonstrated in the cohort of patients with the highest level of regression. Myocardial fibrosis is often seen in patients before intervention, and its presence is associated with worse perioperative and long-term outcome. In this chapter we review the literature pertaining to the importance of myocardial fibrosis in patients with aortic stenosis and evaluate the mechanisms, detection, and clinical significance.
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References
Lindroos M, Kupari M, Heikkilä J, Tilvis R. Prevalence of aortic valve abnormalities in the elderly: an echocardiographic study of a random population sample. J Am Coll Cardiol. 1993;21:1220–5.
Dweck MR, Boon NA, Newby DE. Calcific aortic stenosis: a disease of the valve and the myocardium. J Am Coll Cardiol. 2012;60:1854–63.
Carabello B. The relationship of left ventricular geometry and hypertrophy to left ventricular function in valvular heart disease. J Hear Valve Dis. 1995;S2:S132–8.
Yarbrough W, Mukherjee R, Ikonomidis J, Zile M, Spinale F. NIH public access. J Thorac Cardiovasc Surg. 2012;143:656–64.
Dunning J, Gao H, Chambers J, Moat N, Murphy G, Pagano D, et al. Aortic valve surgery: marked increases in volume and significant decreases in mechanical valve use--an analysis of 41,227 patients over 5 years from the Society for Cardiothoracic Surgery in Great Britain and Ireland National database. J Thorac Cardiovasc Surg. 2011;142:776–82.
Weidemann F, Herrmann S, Störk S, Niemann M, Frantz S, Lange V, et al. Impact of myocardial fibrosis in patients with symptomatic severe aortic stenosis. Circulation. 2009;120:577–84.
Vahanian A, Alfieri O, Andreotti F, Antunes MJ, Barón-Esquivias G, Baumgartner H, et al. Guidelines on the management of valvular heart disease (version 2012). Eur Heart J. 2012;33:2451–96.
Nishimura RA, Otto CM, Bonow RO, Carabello BA, Erwin JP, Guyton RA, et al. 2014 AHA/ACC Guideline for the management of patients with valvular heart disease: executive summary: a report of the American College of Cardiology/American Heart Association task force on practice guidelines. J Am Coll Cardiol. 2014;148:e1–132.
Grossman W, Paulus WJ. Myocardial stress and hypertrophy: a complex interface between biophysics and cardiac remodeling. J Clin Invest. 2013;123:3701–3.
Lorell BH, Carabello BA. Left ventricular hypertrophy: pathogenesis, detection, and prognosis. Circulation. 2000;102:470–9.
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.
Chin CW, Vassiliou V, Jenkins WS, Prasad SK, Newby DE, Dweck MR. Markers of left ventricular decompensation in aortic stenosis. Expert Rev Cardiovasc Ther. 2014;12:901–2.
Dweck MR, Joshi S, Murigu T, Gulati A, Alpendurada F, Jabbour A, et al. Left ventricular remodeling and hypertrophy in patients with aortic stenosis: insights from cardiovascular magnetic resonance. J Cardiovasc Magn Reson. 2012;14:50.
Carroll JD, Carroll EP, Feldman T, Ward DM, Lang RM, McGaughey D, et al. Sex-associated differences in left ventricular function in aortic stenosis of the elderly. Circulation. 1992;86:1099–107.
Villar AV, García R, Merino D, Llano M, Cobo M, Montalvo C, et al. Myocardial and circulating levels of microRNA-21 reflect left ventricular fibrosis in aortic stenosis patients. Int J Cardiol. 2013;167:2875–81.
Douglas PS, Otto CM, Mickel MC, Labovitz A, Reid CL, Davis KB. Gender differences in left ventricle geometry and function in patients undergoing balloon dilatation of the aortic valve for isolated aortic stenosis. NHLBI Balloon Valvuloplasty Registry. Br Heart J. 1995;73:548–54.
Villari B, Campbell SE, Schneider J, Vassalli G, Chiariello M, Hess OM. Sex-dependent differences in left ventricular function and structure in chronic pressure overload. Eur Heart J. 1995;16:1410–9.
Pagé A, Dumesnil JG, Clavel M-A, Chan KL, Teo KK, Tam JW, et al. Metabolic syndrome is associated with more pronounced impairment of left ventricle geometry and function in patients with calcific aortic stenosis: a substudy of the ASTRONOMER (Aortic Stenosis Progression Observation Measuring Effects of Rosuvastatin). J Am Coll Cardiol. 2010;55:1867–74.
Lund BP, Gohlke-Bärwolf C, Cramariuc D, Rossebø AB, Rieck AE, Gerdts E. Effect of obesity on left ventricular mass and systolic function in patients with asymptomatic aortic stenosis (a Simvastatin Ezetimibe in Aortic Stenosis [SEAS] substudy). Am J Cardiol. 2010;105:1456–60.
Rieck AE, Cramariuc D, Staal EM, Rossebø AB, Wachtell K, Gerdts E. Impact of hypertension on left ventricular structure in patients with asymptomatic aortic valve stenosis (a SEAS substudy). J Hypertens. 2010;28:377–83.
Villari B, Hess OM, Kaufmann P, Krogmann ON, Grimm J, Krayenbuehl HP. Effect of aortic valve stenosis (pressure overload) and regurgitation (volume overload) on left ventricular systolic and diastolic function. Am J Cardiol. 1992;69:927–34.
Hein S, Arnon E, Kostin S, Schönburg M, Elsässer A, Polyakova V, et al. Progression from compensated hypertrophy to failure in the pressure-overloaded human heart: structural deterioration and compensatory mechanisms. Circulation. 2003;107:984–91.
Gonzalez A, Lopez B, Ravassa S, Querejeta R, Larman M, Diez J, et al. Stimulation of cardiac apoptosis in essential hypertension: potential role of angiotensin II. Hypertension. 2002;39:75–80.
Weber KT, Brilla CG. Pathological hypertrophy and cardiac interstitium. Fibrosis and renin- angiotensin-aldosterone system. Circulation. 1991;83:1849–65.
Bull S, Loudon M, Francis JM, Joseph J, Gerry S, Karamitsos TD, et al. A prospective, double-blind, randomized controlled trial of the angiotensin-converting enzyme inhibitor Ramipril In Aortic Stenosis (RIAS trial). Eur Hear J Cardiovasc Imaging. 2015;16:834–41.
Singh A, Ford I, Greenwood JP, Khan JN, Uddin A, Berry C, et al. 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. BMJ Open. 2013;3:e004348.
Dobaczewski M, Chen W, Frangogiannis NG. Transforming growth factor (TGF)-β signaling in cardiac remodeling. J Mol Cell Cardiol. 2011;51:600–6.
McCrohon JA, Moon JCC, Prasad SK, McKenna WJ, Lorenz CH, Coats AJ, et al. Differentiation of heart failure related to dilated cardiomyopathy and coronary artery disease using gadolinium-enhanced cardiovascular magnetic resonance. Circulation. 2003;108:54–9.
Mahrholdt H, Wagner A, Judd RM, Sechtem U, Kim RJ. Delayed enhancement cardiovascular magnetic resonance assessment of non-ischaemic cardiomyopathies. Eur Heart J. 2005;26:1461–74.
Stuckey DJ, McSweeney SJ, Thin MZ, Habib J, Price AN, Fiedler LR, et al. T1 mapping detects pharmacological retardation of diffuse cardiac fibrosis in mouse pressure-overload hypertrophy. Circ Cardiovasc Imaging. 2014;7:240–9.
Wong TC, Piehler KM, Kang IA, Kadakkal A, Kellman P, Schwartzman DS, et al. Myocardial extracellular volume fraction quantified by cardiovascular magnetic resonance is increased in diabetes and associated with mortality and incident heart failure admission. Eur Heart J. 2014;35:657–64.
Perk G, Tunick PA, Kronzon I. Non-Doppler two-dimensional strain imaging by echocardiography--from technical considerations to clinical applications. J Am Soc Echocardiogr. 2007;20:234–43.
Mor-Avi V, Lang RM, Badano LP, Belohlavek M, Cardim NM, Derumeaux G, et al. Current and evolving echocardiographic techniques for the quantitative evaluation of cardiac mechanics: ASE/EAE consensus statement on methodology and indications endorsed by the Japanese Society of Echocardiography. J Am Soc Echocardiogr. 2011;24:277–313.
Picano E, Pelosi G, Marzilli M, Lattanzi F, Benassi A, Landini L, et al. In vivo quantitative ultrasonic evaluation of myocardial fibrosis in humans. Circulation. 1990;81:58–64.
Shiozaki AA, Senra T, Arteaga E, Martinelli Filho M, Pita CG, Ávila LFR, et al. Myocardial fibrosis detected by cardiac CT predicts ventricular fibrillation/ventricular tachycardia events in patients with hypertrophic cardiomyopathy. J Cardiovasc Comput Tomogr. 2013;7:173–81.
Bandula S, White SK, Flett AS, Lawrence D, Pugliese F, Ashworth MT, et al. Measurement of myocardial extracellular volume fraction by using equilibrium contrast-enhanced CT: validation against histologic findings. Radiology. 2013;269:396–403.
Serini G, Valdembri D, Bussolino F. Integrins and angiogenesis: a sticky business. Exp Cell Res. 2006;312:651–8.
Jenkins WSA, Chin C, Rudd JHF, Newby DE, Dweck MR. What can we learn about valvular heart disease from PET/CT? Futur Cardiol. 2013;9:657–67.
Dweck MR, Joshi S, Murigu T, Alpendurada F, Jabbour A, Melina G, et al. Midwall fibrosis is an independent predictor of mortality in patients with aortic stenosis. J Am Coll Cardiol. 2011;58:1271–9.
Azevedo CF, Nigri M, Higuchi ML, Pomerantzeff PM, Spina GS, Sampaio RO, 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.
Nazarian S. Is ventricular arrhythmia a possible mediator of the association between aortic stenosis-related midwall fibrosis and mortality? J Am Coll Cardiol. 2011;58:1280–2.
Quarto C, Dweck MR, Murigu T, Joshi S, Melina G, Angeloni E, et al. Late gadolinium enhancement as a potential marker of increased perioperative risk in aortic valve replacement. Interact Cardiovasc Thorac Surg. 2012;15:45–50.
Milano AD, Faggian G, Dodonov M, Golia G, Tomezzoli A, Bortolotti U, et al. Prognostic value of myocardial fibrosis in patients with severe aortic valve stenosis. J Thorac Cardiovasc Surg. 2012;144:830–7.
Barone-Rochette G, Piérard S, De Meester de Ravenstein C, Seldrum S, Melchior J, Maes F, et al. Prognostic significance of LGE by CMR in aortic stenosis patients undergoing valve replacement. J Am Coll Cardiol. 2014;64:144–54.
Messroghli DR, Radjenovic A, Kozerke S, Higgins DM, Sivananthan MU, Ridgway JP. Modified Look-Locker inversion recovery (MOLLI) for high-resolution T1 mapping of the heart. Magn Reson Med. 2004;52:141–6.
Flett AS, Hayward MP, Ashworth MT, Hansen MS, Taylor AM, Elliott PM, et al. Equilibrium contrast cardiovascular magnetic resonance for the measurement of diffuse myocardial fibrosis: preliminary validation in humans. Circulation. 2010;122:138–44.
Chin CWL, Shah ASV, McAllister DA, Joanna Cowell S, Alam S, Langrish JP, et al. High-sensitivity troponin I concentrations are a marker of an advanced hypertrophic response and adverse outcomes in patients with aortic stenosis. Eur Heart J. 2014;35:2312–21.
Vassiliou V, Heng EL, Sharma P, Nyktari E, Raphael CE, Chin CW, et al. Reproducibility of T1 mapping 11-heart beat MOLLI sequence. J Cardiovasc Magn Resonance. 2015;17:W26.
Wong TC, Piehler K, Meier CG, Testa SM, Klock AM, Aneizi AA, et al. Association between extracellular matrix expansion quantified by cardiovascular magnetic resonance and short-term mortality. Circulation. 2012;126:1206–16.
Flett AS, Sado DM, Quarta G, Mirabel M, Pellerin D, Herrey AS, 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.
Sharma UC, Pokharel S, van Brakel TJ, van Berlo JH, Cleutjens JPM, Schroen B, et al. Galectin-3 marks activated macrophages in failure-prone hypertrophied hearts and contributes to cardiac dysfunction. Circulation. 2004;110:3121–8.
Baldenhofer G, Zhang K, Spethmann S, Laule M, Eilers B, Leonhardt F, et al. Galectin-3 predicts short- and long-term outcome in patients undergoing transcatheter aortic valve implantation (TAVI). Int J Cardiol. 2014;177:912–7.
Breyley JG, Novak E, Wittenberg AM, Zajarias A, Maniar H, Damiano R, et al. Soluble St2 is associated with increased mortality and reclassifies risk in patients with severe aortic stenosis. J Am Coll Cardiol. 2014;63:A1920.
Zachariah JP, Colan SD, Lang P, Triedman JK, Alexander ME, Walsh EP, et al. Circulating matrix metalloproteinases in adolescents with hypertrophic cardiomyopathy and ventricular arrhythmia. Circ Heart Fail. 2012;5:462–6.
Tanaka-Esposito C, Varahan S, Jeyaraj D, Lu Y, Stambler BS. Eplerenone-mediated regression of electrical activation delays and myocardial fibrosis in heart failure. J Cardiovasc Electrophysiol. 2014;25:537–44.
Yu L, Ruifrok WPT, Meissner M, Bos EM, van Goor H, Sanjabi B, et al. Genetic and pharmacological inhibition of galectin-3 prevents cardiac remodeling by interfering with myocardial fibrogenesis. Circ Heart Fail. 2013;6:107–17.
Calvier L, Martinez-Martinez E, Miana M, Cachofeiro V, Rousseau E, Sádaba JR, et al. The impact of galectin-3 inhibition on aldosterone-induced cardiac and renal injuries. JACC Heart Fail. 2015;3:59–67.
Mackinnon AC, Gibbons MA, Farnworth SL, Leffler H, Nilsson UJ, Delaine T, et al. Regulation of transforming growth factor-β1-driven lung fibrosis by galectin-3. Am J Respir Crit Care Med. 2012;185:537–46.
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Vassiliou, V.S., Chin, C.W.L., Malley, T., Newby, D.E., Dweck, M.R., Prasad, S.K. (2019). Left Ventricular Fibrosis in Patients with Aortic Stenosis. In: Stanger, O., Pepper, J., Svensson, L. (eds) Surgical Management of Aortic Pathology. Springer, Vienna. https://doi.org/10.1007/978-3-7091-4874-7_8
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