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Current Vascular Pharmacology

Editor-in-Chief

ISSN (Print): 1570-1611
ISSN (Online): 1875-6212

Systematic Review Article

Aortic Stenosis, Aortic Regurgitation and Arterial Hypertension

Author(s): V. Katsi, G. Georgiopoulos*, D. Oikonomou, C. Aggeli , C. Grassos, D.P. Papadopoulos, C. Thomopoulos, M. Marketou, K. Dimitriadis, K. Toutouzas, P. Nihoyannopoulos, C. Tsioufis and D. Tousoulis

Volume 17, Issue 2, 2019

Page: [180 - 190] Pages: 11

DOI: 10.2174/1570161116666180101165306

Price: $65

Abstract

Background: Hypertension (HT) is an important risk factor for cardiovascular disease and might precipitate pathology of the aortic valve.

Objective: To investigate the association of HT with aortic dysfunction (including both aortic regurgitation and stenosis) and the impact of antihypertensive treatment on the natural course of underlying aortic disease.

Methods: We performed a systematic review of the literature for all relevant articles assessing the correlation between HT and phenotype of aortic disease.

Results: Co-existence of HT with aortic stenosis and aortic regurgitation is highly prevalent in hypertensive patients and predicts a worse prognosis. Certain antihypertensive agents may improve haemodynamic parameters (aortic jet velocity, aortic regurgitation volume) and remodeling of the left ventricle, but there is no strong evidence of benefit regarding clinical outcomes. Renin-angiotensin system inhibitors, among other vasodilators, are well-tolerated in aortic stenosis.

Conclusion: Several lines of evidence support a detrimental association between HT and aortic valve disease. Therefore, HT should be promptly treated in aortic valvulopathy. Despite conventional wisdom, specific vasodilators can be used with caution in aortic stenosis.

Keywords: Valvular heart disease, hypertension, blood pressure, aortic valve, aortic stenosis, aortic regurgitation, reninangiotensin system inhibitors.

Graphical Abstract
[1]
Supino PG, Borer JS, Preibisz J, Bornstein A. The epidemiology of valvular heart disease: A growing public health problem. Heart Fail Clin 2006; 2: 379-93.
[2]
Nkomo VT, Gardin JM, Skelton TN, Gottdiener JS, Scott CG, Enriquez-Sarano M. Burden of valvular heart diseases: A population-based study. Lancet 2006; 368: 1005-11.
[3]
Lindroos M, Kupari M, Heikkila 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.
[4]
Eveborn GW, Schirmer H, Lunde P, Heggelund G, Hansen JB, Rasmussen K. Assessment of risk factors for developing incident aortic stenosis: The tromso study. Eur J Epidemiol 2014; 29: 567-75.
[5]
Antonini-Canterin F, Huang G, Cervesato E, et al. Symptomatic aortic stenosis: Does systemic hypertension play an additional role? Hypertensio 2003; 41: 1268-72.
[6]
Tastet L, Capoulade R, Clavel MA, et al. Systolic hypertension and progression of aortic valve calcification in patients with aortic stenosis: Results from the PROGRESSA study. Eur Heart J Cardiovasc Imaging 2017; 18(1): 70-8.
[7]
Hueb JC, Vicentini JT, Roscani MG, et al. Impact of hypertension on ventricular remodeling in patients with aortic stenosis. Arq Bras Cardiol 2011; 97: 254-9.
[8]
Rieck AE, Cramariuc D, Staal EM, Rossebo AB, Wachtell K, Gerdts E. Impact of hypertension on left ventricular structure in patients with asymptomatic aortic valve stenosis (a SEAS sub study). J Hypertens 2010; 28: 377-83.
[9]
Rieck AE, Cramariuc D, Boman K, et al. Hypertension in aortic stenosis: Implications for left ventricular structure and cardiovascular events. Hypertension 2012; 60: 90-7.
[10]
Briand M, Dumesnil JG, Kadem L, et al. Reduced systemic arterial compliance impacts significantly on left ventricular afterload and function in aortic stenosis: Implications for diagnosis and treatment. J Am Coll Cardiol 2005; 46: 291-8.
[11]
Yan AT, Koh M, Chan KK, et al. Association between cardiovascular risk factors and aortic stenosis: The CANHEART Aortic Stenosis Study. J Am Coll Cardiol 2017; 69: 1523-32.
[12]
Baumgartner H, Hung J, Bermejo J, et al. Echocardiographic assessment of valve stenosis: EAE/ASE recommendations for clinical practice. J Am Soc Echocardiogr 2009; 22: 1-23.
[13]
Pasipoularides A. Clinical assessment of ventricular ejection dynamics with and without outflow obstruction. J Am Coll Cardiol 1990; 15: 859-82.
[14]
Bermejo J, Rojo-Alvarez JL, Antoranz JC, et al. Estimation of the end of ejection in aortic stenosis: An unreported source of error in the invasive assessment of severity. Circulation 2004; 110: 1114-20.
[15]
Laskey WK, Kussmaul WG, Noordergraaf A. Valvular and systemic arterial hemodynamics in aortic valve stenosis. A model-based approach. Circulation 1995; 92: 1473-8.
[16]
Razzolini R, Gerosa G, Leoni L, Casarotto D, Chioin R, Dalla-Volta S. Transaortic gradient is pressure-dependent in a pulsatile model of the circulation. J Heart Valve Dis 1999; 8: 279-83.
[17]
Mascherbauer J, Fuchs C, Stoiber M, et al. Systemic pressure does not directly affect pressure gradient and valve area estimates in aortic stenosis in vitro. Eur Heart J 2008; 29: 2049-57.
[18]
Kadem L, Dumesnil JG, Rieu R, Durand LG, Garcia D, Pibarot P. Impact of systemic hypertension on the assessment of aortic stenosis. Heart 2005; 91: 354-61.
[19]
Little SH, Chan KL, Burwash IG. Impact of blood pressure on the Doppler echocardiographic assessment of severity of aortic stenosis. Heart 2007; 93: 848-55.
[20]
Cote N, Simard L, Zenses AS, et al. Impact of vascular hemodynamics on aortic stenosis evaluation: New insights into the pathophysiology of normal flow-small aortic valve area-low gradient pattern. J Am Heart Assoc 2017; 6(7): e006276.
[21]
Pachulski RT, Chan KL. Progression of aortic valve dysfunction in 51 adult patients with congenital bicuspid aortic valve: Assessment and follow up by Doppler echocardiography. Br Heart J 1993; 69: 237-40.
[22]
Olsson M, Dalsgaard CJ, Haegerstrand A, Rosenqvist M, Ryden L, Nilsson J. Accumulation of T lymphocytes and expression of interleukin-2 receptors in nonrheumatic stenotic aortic valves. J Am Coll Cardiol 1994; 23: 1162-70.
[23]
O’Brien KD, Reichenbach DD, Marcovina SM, Kuusisto J, Alpers CE, Otto CM. Apolipoproteins B, (a), and E accumulate in the morphologically early lesion of ‘degenerative’ valvular aortic stenosis. Arterioscler Thromb Vasc Biol 1996; 16: 523-32.
[24]
Mohler ER 3rd, Gannon F, Reynolds C, Zimmerman R, Keane MG, Kaplan FS. Bone formation and inflammation in cardiac valves. Circulation 2001; 103: 1522-8.
[25]
O’Brien KD, Shavelle DM, Caulfield MT, et al. Association of angiotensin-converting enzyme with low-density lipoprotein in aortic valvular lesions and in human plasma. Circulation 2002; 106: 2224-30.
[26]
Pibarot P, Dumesnil JG. Assessment of aortic stenosis severity: Check the valve but don’t forget the arteries! Heart 2007; 93: 780-2.
[27]
Nguyen V, Cimadevilla C, Estellat C, et al. Haemodynamic and anatomic progression of aortic stenosis. Heart 2015; 101: 943-7.
[28]
Clavel MA, Pibarot P, Messika-Zeitoun D, et al. Impact of aortic valve calcification, as measured by MDCT, on survival in patients with aortic stenosis: Results of an international registry study. J Am Coll Cardiol 2014; 64: 1202-13.
[29]
Thomassen HK, Cioffi G, Gerdts E, et al. Echocardiographic aortic valve calcification and outcomes in women and men with aortic stenosis. Heart 2017; 103: 1619-24.
[30]
Thubrikar MJ, Aouad J, Nolan SP. Patterns of calcific deposits in operatively excised stenotic or purely regurgitant aortic valves and their relation to mechanical stress. Am J Cardiol 1986; 58: 304-8.
[31]
Stewart BF, Siscovick D, Lind BK, et al. Clinical factors associated with calcific aortic valve disease. J Am Coll Cardiol 1997; 29: 630-4.
[32]
Ferreira-Gonzalez I, Pinar-Sopena J, Ribera A, et al. Prevalence of calcific aortic valve disease in the elderly and associated risk factors: A population-based study in a Mediterranean area. Eur J Prev Cardiol 2013; 20: 1022-30.
[33]
Linefsky J, Katz R, Budoff M, et al. Stages of systemic hypertension and blood pressure as correlates of computed tomography-assessed aortic valve calcium (from the Multi-Ethnic Study of Atherosclerosis). Am J Cardiol 2011; 107: 47-51.
[34]
ten Kate GJ, Bos S, Dedic A, et al. Increased aortic valve calcification in familial hypercholesterolemia: Prevalence, extent, and associated risk factors. J Am Coll Cardiol 2015; 66: 2687-95.
[35]
Iwata S, Russo C, Jin Z, et al. Higher ambulatory blood pressure is associated with aortic valve calcification in the elderly: A population-based study. Hypertension 2013; 61: 55-60.
[36]
Capoulade R, Clavel MA, Mathieu P, et al. Impact of hypertension and renin-angiotensin system inhibitors in aortic stenosis. Eur J Clin Invest 2013; 43: 1262-72.
[37]
Eleid MF, Nishimura RA, Sorajja P, Borlaug BA. Systemic hypertension in low-gradient severe aortic stenosis with preserved ejection fraction. Circulation 2013; 128: 1349-53.
[38]
Levy D, Garrison RJ, Savage DD, Kannel WB, Castelli WP. Prognostic implications of echocardiographically determined left ventricular mass in the Framingham Heart Study. N Engl J Med 1990; 322: 1561-6.
[39]
Katsi V, Marketou M, Kallistratos MS, et al. Aortic valve stenosis and arterial hypertension: A synopsis in 2013. Curr Hypertens Rep 2013; 15: 298-303.
[40]
Tuseth N, Cramariuc D, Rieck AE, Wachtell K, Gerdts E. Asymmetric septal hypertrophy - a marker of hypertension in aortic stenosis (a SEAS substudy). Blood Press 2010; 19: 140-4.
[41]
Haering JM, Comunale ME, Parker RA, et al. Cardiac risk of noncardiac surgery in patients with asymmetric septal hypertrophy. Anesthesiology 1996; 85: 254-9.
[42]
Garcia D, Pibarot P, Kadem L, Durand LG. Respective impacts of aortic stenosis and systemic hypertension on left ventricular hypertrophy. J Biomech 2007; 40: 972-80.
[43]
Li JK, Zhu JY, Nanna M. Computer modeling of the effects of aortic valve stenosis and arterial system afterload on left ventricular hypertrophy. Comput Biol Med 1997; 27: 477-85.
[44]
Ashikhmina EA, Schaff HV, Dearani JA, et al. Aortic valve replacement in the elderly: Determinants of late outcome. Circulation 2011; 124: 1070-8.
[45]
Imanaka K, Kohmoto O, Nishimura S, Yokote Y, Kyo S. Impact of postoperative blood pressure control on regression of left ventricular mass following valve replacement for aortic stenosis. Eur J Cardiothorac Surg 2005; 27: 994-9.
[46]
Gavina C, Falcao-Pires I, Rodrigues J, et al. Load independent impairment of reverse remodeling after valve replacement in hypertensive aortic stenosis patients. Int J Cardiol 2014; 170: 324-30.
[47]
Lund O, Emmertsen K, Dorup I, Jensen FT, Flo C. Regression of left ventricular hypertrophy during 10 years after valve replacement for aortic stenosis is related to the preoperative risk profile. Eur Heart J 2003; 24: 1437-46.
[48]
Bove T, Van Belleghem Y, Francois K, Caes F, Van Overbeke H, Van Nooten G. Stentless and stented aortic valve replacement in elderly patients: Factors affecting midterm clinical and hemodynamical outcome. Eur J Cardiothorac Surg 2006; 30: 706-13.
[49]
Helder MR, Ugur M, Bavaria JE, et al. The effect of postoperative medical treatment on left ventricular mass regression after aortic valve replacement. J Thorac Cardiovasc Surg 2015; 149: 781-6.
[50]
Gaudino M, Alessandrini F, Glieca F, et al. Survival after aortic valve replacement for aortic stenosis: does left ventricular mass regression have a clinical correlate? Eur Heart J 2005; 26: 51-7.
[51]
Cramariuc D, Gerdts E, Segadal L. Impact of hypertension on left ventricular hypertrophy regression and exercise capacity in patients operated for aortic valve stenosis. Scand Cardiovasc J 2006; 40: 167-74.
[52]
Vanky FB, Hakanson E, Tamas E, Svedjeholm R. Risk factors for postoperative heart failure in patients operated on for aortic stenosis. Ann Thorac Surg 2006; 81: 1297-304.
[53]
Reinthaler M, Stahli BE, Gopalamurugan AB, et al. Post-procedural arterial hypertension: Implications for clinical outcome after transcatheter aortic valve implantation. J Heart Valve Dis 2014; 23: 675-82.
[54]
Perlman GY, Loncar S, Pollak A, et al. Post-procedural hypertension following transcatheter aortic valve implantation: Incidence and clinical significance. JACC Cardiovasc Interv 2013; 6: 472-8.
[55]
Yotti R, Bermejo J, Gutierrez-Ibanes E, et al. Systemic vascular load in calcific degenerative aortic valve stenosis: Insight from percutaneous valve replacement. J Am Coll Cardiol 2015; 65: 423-33.
[56]
Dalsgaard M, Iversen K, Kjaergaard J, et al. Short-term hemodynamic effect of angiotensin-converting enzyme inhibition in patients with severe aortic stenosis: a placebo-controlled, randomized study. Am Heart J 2014; 167: 226-34.
[57]
Khot UN, Novaro GM, Popovic ZB, et al. Nitroprusside in critically ill patients with left ventricular dysfunction and aortic stenosis. N Engl J Med 2003; 348: 1756-63.
[58]
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: 149-54.
[59]
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 Thorac Cardiovasc Surg 2014; 148: 1-132.
[60]
Helske S, Lindstedt KA, Laine M, et al. Induction of local angiotensin II-producing systems in stenotic aortic valves. J Am Coll Cardiol 2004; 44: 1859-66.
[61]
Fielitz J, Hein S, Mitrovic V, et al. Activation of the cardiac renin-angiotensin system and increased myocardial collagen expression in human aortic valve disease. J Am Coll Cardiol 2001; 37: 1443-9.
[62]
Cowan BR, Young AA. Left ventricular hypertrophy and renin-angiotensin system blockade. Curr Hypertens Rep 2009; 11: 167-72.
[63]
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: 19.
[64]
Bang CN, Greve AM, Kober L, et al. Renin-angiotensin system inhibition is not associated with increased sudden cardiac death, cardiovascular mortality or all-cause mortality in patients with aortic stenosis. Int J Cardiol 2014; 175: 492-8.
[65]
O’Brien KD, Zhao XQ, Shavelle DM, et al. Hemodynamic effects of the angiotensin-converting enzyme inhibitor, ramipril, in patients with mild to moderate aortic stenosis and preserved left ventricular function. J Investig Med 2004; 52: 185-91.
[66]
Rosenhek R, Rader F, Loho N, et al. Statins but not angiotensin-converting enzyme inhibitors delay progression of aortic stenosis. Circulation 2004; 110: 1291-5.
[67]
Ardehali R, Leeper NJ, Wilson AM, Heidenreich PA. The effect of angiotensin-converting enzyme inhibitors and statins on the progression of aortic sclerosis and mortality. J Heart Valve Dis 2012; 21: 337-43.
[68]
Wakabayashi K, Tsujino T, Naito Y, et al. Administration of angiotensin-converting enzyme inhibitors is associated with slow progression of mild aortic stenosis in Japanese patients. Heart Vessels 2011; 26: 252-7.
[69]
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: 570-6.
[70]
Bull S, Loudon M, Francis JM, et al. A prospective, double-blind, randomized controlled trial of the angiotensin-converting enzyme inhibitor Ramipril in aortic stenosis (RIAS trial). Eur Heart J Cardiovasc Imaging 2015; 16: 834-41.
[71]
Andersson C, Abdulla J. Is the use of Renin-angiotensin system inhibitors in patients with aortic valve stenosis safe and of prognostic benefit? a systematic review and meta-analysis. Eur Heart J Cardiovasc Pharmacother 2017; 3(1): 21-7.
[72]
Grimard BH, Safford RE, Burns EL. Aortic stenosis: Diagnosis and treatment. Am Fam Physician 2016; 93: 371-8.
[73]
Pai RG, Kapoor N, Bansal RC, Varadarajan P. Malignant natural history of asymptomatic severe aortic stenosis: Benefit of aortic valve replacement. Ann Thorac Surg 2006; 82: 2116-22.
[74]
Mostafa A, El-Haddad MA, Shenoy M, Tuliani T. Atrial fibrillation post cardiac bypass surgery. Avicenna J Med 2012; 2: 65-70.
[75]
Stouffer GA, Uretsky BF. Hemodynamic changes of aortic regurgitation. Am J Med Sci 1997; 314: 411-4.
[76]
Singh JP, Evans JC, Levy D, et al. Prevalence and clinical determinants of mitral, tricuspid, and aortic regurgitation (the Framingham Heart Study). Am J Cardiol 1999; 83: 897-902.
[77]
Palmieri V, Bella JN, Arnett DK, et al. Aortic root dilatation at sinuses of valsalva and aortic regurgitation in hypertensive and normotensive subjects: The hypertension genetic epidemiology network study. Hypertension 2001; 37: 1229-35.
[78]
Stefano G, Fox K, Schluchter M, Hoit BD. Prevalence of unsuspected and significant mitral and aortic regurgitation. J Am Soc Echocardiogr 2008; 21: 38-42.
[79]
Gardin JM, Constantine G, Davis K, Leung C, Reid CL. Aortic valvular regurgitation: Prevalence and clinical characteristics in a predominantly obese adult population not taking anorexigens. Echocardiography 2006; 23: 569-76.
[80]
Lebowitz NE, Bella JN, Roman MJ, et al. Prevalence and correlates of aortic regurgitation in American Indians: The strong heart study. J Am Coll Cardiol 2000; 36: 461-7.
[81]
Vigna C, Russo A, Salvatori MP, et al. Color and pulsed-wave Doppler study of aortic regurgitation in systemic hypertension. Am J Cardiol 1988; 61: 928-9.
[82]
Morita H, Mizushige K, Fukada H, Senda S, Matsuo H. Evaluation of left-sided valvular regurgitation in healthy, hypertensive and myocardial infarction subjects by Doppler echocardiography. Jpn Circ J 1990; 54: 292-7.
[83]
Lonati L, Cuspidi C, Sampieri L, et al. Prevalence of physiological valvular regurgitation in hypertensive patients: Echocardiographic and color Doppler study. Cardiology 1992; 81: 365-70.
[84]
Maurer G. Aortic regurgitation. Heart 2006; 92: 994-1000.
[85]
Kim M, Roman MJ, Cavallini MC, Schwartz JE, Pickering TG, Devereux RB. Effect of hypertension on aortic root size and prevalence of aortic regurgitation. Hypertension 1996; 28: 47-52.
[86]
Jakrapanichakul D, Chirakarnjanakorn S. Comparison of aortic diameter in normal subjects and patients with systemic hypertension. J Med Assoc Thai 2011; 94(Suppl. 1): 51-6.
[87]
Ravakhah K, Motallebi M. Silent aortic regurgitation in systemic hypertension. J Heart Valve Dis 2013; 22: 64-70.
[88]
Mizariene V, Bucyte S, Zaliaduonyte-Peksiene D, Jonkaitiene R, Vaskelyte J, Jurkevicius R. Left ventricular mechanics in asymptomatic normotensive and hypertensive patients with aortic regurgitation. J Am Soc Echocardiogr 2011; 24: 385-91.
[89]
Supino PG, Borer JS, Herrold EM, et al. Prognostic impact of systolic hypertension on asymptomatic patients with chronic severe aortic regurgitation and initially normal left ventricular performance at rest. Am J Cardiol 2005; 96: 964-70.
[90]
Patil NP, Mohite PN, Sabashnikov A, et al. Does postoperative blood pressure influence development of aortic regurgitation following continuous-flow left ventricular assist device implantation?dagger. Eur J Cardiothorac Surg 2016; 49: 788-94.
[91]
Elder DH, Wei L, Szwejkowski BR, et al. The impact of renin-angiotensin-aldosterone system blockade on heart failure outcomes and mortality in patients identified to have aortic regurgitation: A large population cohort study. J Am Coll Cardiol 2011; 58: 2084-91.
[92]
Lin M, Chiang HT, Lin SL, et al. Vasodilator therapy in chronic asymptomatic aortic regurgitation: Enalapril versus hydralazine therapy. J Am Coll Cardiol 1994; 24: 1046-53.
[93]
Plante E, Gaudreau M, Lachance D, et al. Angiotensin-converting enzyme inhibitor captopril prevents volume overload cardiomyopathy in experimental chronic aortic valve regurgitation. Can J Physiol Pharmacol 2004; 82: 191-9.
[94]
Plante E, Lachance D, Champetier S, et al. Benefits of long-term beta-blockade in experimental chronic aortic regurgitation. Am J Physiol Heart Circ Physiol 2008; 294: 1888-95.
[95]
Handler J. Treatment of systolic hypertension and severe asymptomatic aortic regurgitation. J Clin Hypertens (Greenwich) 2008; 10: 951-5.
[96]
Greenberg BH, DeMots H, Murphy E, Rahimtoola S. Beneficial effects of hydralazine on rest and exercise hemodynamics in patients with chronic severe aortic insufficiency. Circulation 1980; 62: 49-55.
[97]
Shen WF, Roubin GS, Hirasawa K, et al. Noninvasive assessment of acute effects of nifedipine on rest and exercise hemodynamics and cardiac function in patients with aortic regurgitation. J Am Coll Cardiol 1984; 4: 902-7.
[98]
Scognamiglio R, Fasoli G, Visintin L, Dalla-Volta S. Effects of unloading and positive inotropic interventions on left ventricular function in asymptomatic patients with chronic severe aortic insufficiency. Clin Cardiol 1987; 10: 804-10.
[99]
Fioretti P, Benussi B, Scardi S, Klugmann S, Brower RW, Camerini F. Afterload reduction with nifedipine in aortic insufficiency. Am J Cardiol 1982; 49: 1728-32.
[100]
Rothlisberger C, Sareli P, Wisenbaugh T. Comparison of single-dose nifedipine and captopril for chronic severe aortic regurgitation. Am J Cardiol 1993; 72: 799-804.
[101]
Scognamiglio R, Rahimtoola SH, Fasoli G, Nistri S, Dalla Volta S. Nifedipine in asymptomatic patients with severe aortic regurgitation and normal left ventricular function. N Engl J Med 1994; 331: 689-94.
[102]
Sondergaard L, Aldershvile J, Hildebrandt P, Kelbaek H, Stahlberg F, Thomsen C. Vasodilatation with felodipine in chronic asymptomatic aortic regurgitation. Am Heart J 2000; 139: 667-74.
[103]
Evangelista A, Tornos P, Sambola A, Permanyer-Miralda G, Soler-Soler J. Long-term vasodilator therapy in patients with severe aortic regurgitation. N Engl J Med 2005; 353: 1342-9.
[104]
Sampat U, Varadarajan P, Turk R, Kamath A, Khandhar S, Pai RG. Effect of beta-blocker therapy on survival in patients with severe aortic regurgitation results from a cohort of 756 patients. J Am Coll Cardiol 2009; 54: 452-7.

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