Aortic stenosis natural history, complications and prognosis: Difference between revisions

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| [[File:Siren.gif|30px|link=Aortic stenosis resident survival guide]]|| <br> || <br>
| [[Aortic stenosis resident survival guide|'''Resident'''<br>'''Survival'''<br>'''Guide''']]
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{{Aortic stenosis}}
{{Aortic stenosis}}
{{CMG}}; '''Associate Editors-In-Chief: '''[[User:Mohammed Sbeih|Mohammed A. Sbeih, M.D.]] [mailto:msbeih@perfuse.org]; {{LG}}
{{CMG}}; '''Associate Editors-In-Chief: '''[[User:Mohammed Sbeih|Mohammed A. Sbeih, M.D.]] [mailto:msbeih@wikidoc.org]; {{LG}}; {{USAMA}}


==Overview==
==Overview==
Left untreated, aortic valve stenosis can lead to [[angina]], [[syncope]], [[congestive heart failure]], [[atrial fibrillation]], [[endocarditis]], and [[sudden cardiac death]].  Surgical treatment of aortic stenosis also carries risks and potential complications including vascular complications and [[mitral valve]] injury.
Left untreated, aortic valve stenosis can lead to [[angina]], [[syncope]], [[congestive heart failure]], [[atrial fibrillation]], [[endocarditis]], and [[sudden cardiac death]].  Surgical treatment of aortic stenosis also carries risks and potential complications that include vascular complications and [[mitral valve]] injury. When aortic stenosis is left untreated, the average survival is 5 years after the onset of [[angina]], 3 years after the onset of [[syncope]], and 1 year after the onset of [[congestive heart failure]].<ref name="pmid4894151">{{cite journal| author=Ross J, Braunwald E| title=Aortic stenosis. | journal=Circulation | year= 1968 | volume= 38 | issue= 1 Suppl | pages= 61-7 | pmid=4894151 | doi= | pmc= | url= }} </ref><ref name="pmid3337000">{{cite journal| author=Kelly TA, Rothbart RM, Cooper CM, Kaiser DL, Smucker ML, Gibson RS| title=Comparison of outcome of asymptomatic to symptomatic patients older than 20 years of age with valvular aortic stenosis. | journal=Am J Cardiol | year= 1988 | volume= 61 | issue= 1 | pages= 123-30 | pmid=3337000 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3337000  }} </ref><ref name="pmid8712130">{{cite journal| author=Iivanainen AM, Lindroos M, Tilvis R, Heikkilä J, Kupari M| title=Natural history of aortic valve stenosis of varying severity in the elderly. | journal=Am J Cardiol | year= 1996 | volume= 78 | issue= 1 | pages= 97-101 | pmid=8712130 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8712130  }} </ref>


==Natural History==
==Natural History, Complications, and Prognosis==
===Calcific Degenerative Aortic Stenosis===
===Natural History===
Aortic stenosis due to degeneration of a calcified aortic valve has a prolonged latent period during which time symptoms may be minimal or even lacking <ref name="pmid8701905">{{cite journal| author=Faggiano P, Aurigemma GP, Rusconi C, Gaasch WH| title=Progression of valvular aortic stenosis in adults: literature review and clinical implications. | journal=Am Heart J | year= 1996 | volume= 132 | issue= 2 Pt 1 | pages= 408-17 | pmid=8701905 | doi= | pmc= | url= }} </ref>. The average rate of progression in valvular aortic stenosis, once moderate stenosis is present and symptomatic, is a decrease in valve area of 0.1 cm<sup>2</sup> per year <ref name="pmid12835667">{{cite journal| author=Zoghbi WA, Enriquez-Sarano M, Foster E, Grayburn PA, Kraft CD, Levine RA et al.| title=Recommendations for evaluation of the severity of native valvular regurgitation with two-dimensional and Doppler echocardiography. | journal=J Am Soc Echocardiogr | year= 2003 | volume= 16 | issue= 7 | pages= 777-802 | pmid=12835667 | doi=10.1016/S0894-7317(03)00335-3 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12835667  }} </ref><ref name="pmid8701905">{{cite journal| author=Faggiano P, Aurigemma GP, Rusconi C, Gaasch WH| title=Progression of valvular aortic stenosis in adults: literature review and clinical implications. | journal=Am Heart J | year= 1996 | volume= 132 | issue= 2 Pt 1 | pages= 408-17 | pmid=8701905 | doi= | pmc= | url= }} </ref>. Also on average, there is an increase in the jet velocity of 0.3 m / second per year and an increase in the mean pressure gradient of 7 mm Hg per year <ref name="pmid495418">{{cite journal| author=Cheitlin MD, Gertz EW, Brundage BH, Carlson CJ, Quash JA, Bode RS| title=Rate of progression of severity of valvular aortic stenosis in the adult. | journal=Am Heart J | year= 1979 | volume= 98 | issue= 6 | pages= 689-700 | pmid=495418 | doi= | pmc= | url= }} </ref> <ref name="pmid6829320">{{cite journal| author=Jonasson R, Jonsson B, Nordlander R, Orinius E, Szamosi A| title=Rate of progression of severity of valvular aortic stenosis. | journal=Acta Med Scand | year= 1983 | volume= 213 | issue= 1 | pages= 51-4 | pmid=6829320 | doi= | pmc= | url= }} </ref><ref name="pmid8404089">{{cite journal| author=Peter M, Hoffmann A, Parker C, Lüscher T, Burckhardt D| title=Progression of aortic stenosis. Role of age and concomitant coronary artery disease. | journal=Chest | year= 1993 | volume= 103 | issue= 6 | pages= 1715-9 | pmid=8404089 | doi= | pmc= | url= }} </ref>. There is tremendous individual variability in the rate of progression of aortic stenosis. Risk factors for [[atherosclerosis]], such as age, smoking, [[hypertension]], obesity and [[diabetes]], lipid abnormalities, chronic [[renal failure]] and dialysis, and atherosclerotic disease itself, such as concomitant [[coronary artery disease]] are associated with more rapid rates of aortic stenosis progression.


===Bicuspid Aortic Valve Disease===
====Degenerative Calcific Aortic Stenosis====
[[Bicuspid aortic valve stenosis]] presents one to two decades earlier.  The rate of progression of degenerative aortic stenosis can be faster than in those with [[congenital]] or [[rheumatic]] disease <ref name="pmid10965007">{{cite journal| author=Rosenhek R, Binder T, Porenta G, Lang I, Christ G, Schemper M et al.| title=Predictors of outcome in severe, asymptomatic aortic stenosis. | journal=N Engl J Med | year= 2000 | volume= 343 | issue= 9 | pages= 611-7 | pmid=10965007 | doi=10.1056/NEJM200008313430903 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10965007  }} </ref>.


===Aortic Sclerosis===
* Aortic stenosis due to the degeneration of a calcified aortic valve has a prolonged latent period during which symptoms are minimal or even lacking. This form of aortic stenosis presents later in life, usually after the age of 75. <ref>Townsend CM, et al. Sabiston Textbook of Surgery. 18th ed. Saunders; 2008:1841-1844.</ref><ref name="pmid8701905">{{cite journal| author=Faggiano P, Aurigemma GP, Rusconi C, Gaasch WH| title=Progression of valvular aortic stenosis in adults: literature review and clinical implications. | journal=Am Heart J | year= 1996 | volume= 132 | issue= 2 Pt 1 | pages= 408-17 | pmid=8701905 | doi= | pmc= | url= }} </ref>
[[Aortic sclerosis]] (defined as [[aortic valve]] thickening without obstruction to ventricular outflow) may progress to narrowing of the aortic valve or [[aortic stenosis]].  If the pulse pressure or upstroke of the pulse diminishes in the patient with aortic sclerosis, this can be a sign of progression to aortic stenosis.
* Once moderate aortic stenosis is present and symptomatic, the average rate of progression of the valvular stenosis is a decrease in the valve area of 0.1 cm<sup>2</sup> per year.<ref name="pmid8701905">{{cite journal| author=Faggiano P, Aurigemma GP, Rusconi C, Gaasch WH| title=Progression of valvular aortic stenosis in adults: literature review and clinical implications. | journal=Am Heart J | year= 1996 | volume= 132 | issue= 2 Pt 1 | pages= 408-17 | pmid=8701905 | doi= | pmc= | url= }} </ref><ref name="pmid19130998">{{cite journal| author=Baumgartner H, Hung J, Bermejo J, Chambers JB, Evangelista A, Griffin BP et al.| title=Echocardiographic assessment of valve stenosis: EAE/ASE recommendations for clinical practice. | journal=J Am Soc Echocardiogr | year= 2009 | volume= 22 | issue= 1 | pages= 1-23; quiz 101-2 | pmid=19130998 | doi=10.1016/j.echo.2008.11.029 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19130998  }} </ref>
* In addition, there is an increase in the jet velocity of 0.3 m/second per year and an increase in the mean pressure gradient of 7 mm Hg per year.<ref name="pmid495418">{{cite journal| author=Cheitlin MD, Gertz EW, Brundage BH, Carlson CJ, Quash JA, Bode RS| title=Rate of progression of severity of valvular aortic stenosis in the adult. | journal=Am Heart J | year= 1979 | volume= 98 | issue= 6 | pages= 689-700 | pmid=495418 | doi= | pmc= | url= }} </ref><ref name="pmid6829320">{{cite journal| author=Jonasson R, Jonsson B, Nordlander R, Orinius E, Szamosi A| title=Rate of progression of severity of valvular aortic stenosis. | journal=Acta Med Scand | year= 1983 | volume= 213 | issue= 1 | pages= 51-4 | pmid=6829320 | doi= | pmc= | url= }} </ref><ref name="pmid8404089">{{cite journal| author=Peter M, Hoffmann A, Parker C, Lüscher T, Burckhardt D| title=Progression of aortic stenosis. Role of age and concomitant coronary artery disease. | journal=Chest | year= 1993 | volume= 103 | issue= 6 | pages= 1715-9 | pmid=8404089 | doi= | pmc= | url= }} </ref>
* There is a tremendous individual variability in the rate of progression of aortic stenosis. Risk factors for [[atherosclerosis]] (such as age, smoking, [[hypertension]], obesity and [[diabetes]], lipid abnormalities, chronic [[renal failure]] and [[dialysis]]) and atherosclerotic disease itself (such as concomitant [[coronary artery disease]]) are associated with more rapid rates of progression of the severity of the aortic stenosis.<ref name="pmid1841025">{{cite journal| author=Mohler ER, Sheridan MJ, Nichols R, Harvey WP, Waller BF| title=Development and progression of aortic valve stenosis: atherosclerosis risk factors--a causal relationship? A clinical morphologic study. | journal=Clin Cardiol | year= 1991 | volume= 14 | issue= 12 | pages= 995-9 | pmid=1841025 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1841025  }} </ref>


==Complications==
====Aortic Stenosis Due to Rheumatic Heart Disease====
*The aortic stenosis due to rheumatic heart disease is amongst the most common causes of aortic stenosis. It is calculated to be around 24% of the total [[prevalence]].<ref name="pmid3807436">{{cite journal| author=Passik CS, Ackermann DM, Pluth JR, Edwards WD| title=Temporal changes in the causes of aortic stenosis: a surgical pathologic study of 646 cases. | journal=Mayo Clin Proc | year= 1987 | volume= 62 | issue= 2 | pages= 119-23 | pmid=3807436 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3807436  }} </ref>
 
====Bicuspid Aortic Valve Disease====
* [[Bicuspid aortic valve stenosis]] presents one or two decades earlier than the tricuspid aortic valve.
* The rate of progression of degenerative aortic stenosis can be faster in patients with [[bicuspid aortic valve]] than in those with [[congenital]] or [[rheumatic]] disease.<ref name="pmid22477390">{{cite journal| author=Kamath AR, Pai RG| title=Risk factors for progression of calcific aortic stenosis and potential therapeutic targets. | journal=Int J Angiol | year= 2008 | volume= 17 | issue= 2 | pages= 63-70 | pmid=22477390 | doi= | pmc=2728414 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22477390  }} </ref><ref name="pmid10965007">{{cite journal| author=Rosenhek R, Binder T, Porenta G, Lang I, Christ G, Schemper M et al.| title=Predictors of outcome in severe, asymptomatic aortic stenosis. | journal=N Engl J Med | year= 2000 | volume= 343 | issue= 9 | pages= 611-7 | pmid=10965007 | doi=10.1056/NEJM200008313430903 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10965007  }} </ref>
* [[Bicuspid aortic valve]] functions without any significant pressure gradient during childhood. However, the thickening and calcification of the valves may be detectable pathologically and on [[echocardiography]] by the second decade.<ref name="pmid8427176">{{cite journal |author=Beppu S, Suzuki S, Matsuda H, Ohmori F, Nagata S, Miyatake K |title=Rapidity of progression of aortic stenosis in patients with congenital bicuspid aortic valves |journal=[[The American Journal of Cardiology]] |volume=71 |issue=4 |pages=322–7 |year=1993 |month=February |pmid=8427176 |doi= |url= |accessdate=2012-04-09}}</ref>
* Approximately 75% of bicuspid aortic valves progress into aortic stenosis requiring operative correction.<ref name="pmid835475">{{cite journal |author=Fenoglio JJ, McAllister HA, DeCastro CM, Davia JE, Cheitlin MD |title=Congenital bicuspid aortic valve after age 20 |journal=[[The American Journal of Cardiology]] |volume=39 |issue=2 |pages=164–9 |year=1977 |month=February |pmid=835475 |doi= |url= |accessdate=2012-04-10}}</ref><ref name="pmid15723989">{{cite journal |author=Lewin MB, Otto CM |title=The bicuspid aortic valve: adverse outcomes from infancy to old age |journal=[[Circulation]] |volume=111 |issue=7 |pages=832–4 |year=2005 |month=February |pmid=15723989 |doi=10.1161/01.CIR.0000157137.59691.0B |url=http://circ.ahajournals.org/cgi/pmidlookup?view=long&pmid=15723989 |accessdate=2012-04-10}}</ref>
* Bicuspid aortic stenosis progressively leads to [[heart failure]], [[arrythmias]], [[angina]] and other [[symptoms]]. These symptoms generally manifests between 40 to 60 years of age, which is relatively a younger age than that of the manifestation of the [[symptoms]] caused by aortic stenosis. However, children who develop early pathological changes in bicuspid aortic valve are more likely to develop [[Aortic regurgitation|aortic insufficiency]] than stenosis.<ref name="pmid835475">{{cite journal |author=Fenoglio JJ, McAllister HA, DeCastro CM, Davia JE, Cheitlin MD |title=Congenital bicuspid aortic valve after age 20 |journal=[[The American Journal of Cardiology]] |volume=39 |issue=2 |pages=164–9 |year=1977 |month=February |pmid=835475 |doi= |url= |accessdate=2012-04-10}}</ref>
 
====Aortic Sclerosis====
*[[Aortic sclerosis]] (defined as [[aortic valve]] thickening without obstruction to ventricular outflow) may progress to narrowing of the aortic valve or [[aortic stenosis]].  The decrease in pulse pressure or upstroke of the pulse in a patient with aortic sclerosis is a sign of progression to aortic stenosis.<ref name="pmid27543711">{{cite journal| author=Di Minno MN, Di Minno A, Songia P, Ambrosino P, Gripari P, Ravani A et al.| title=Markers of subclinical atherosclerosis in patients with aortic valve sclerosis: A meta-analysis of literature studies. | journal=Int J Cardiol | year= 2016 | volume= 223 | issue=  | pages= 364-370 | pmid=27543711 | doi=10.1016/j.ijcard.2016.08.122 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27543711  }} </ref>
 
===Complications===
====Degenerative Calcific Aortic Stenosis====
If left untreated, aortic stenosis may lead to complications such as [[angina]], [[syncope]], or [[heart failure]].
If left untreated, aortic stenosis may lead to complications such as [[angina]], [[syncope]], or [[heart failure]].
A complete list of complications of aortic stenosis includes the following:<ref>{{Cite journal
| author = [[S. Frank]], [[A. Johnson]] & [[J. Jr Ross]]
| title = Natural history of valvular aortic stenosis
| journal = [[British heart journal]]
| volume = 35
| issue = 1
| pages = 41–46
| year = 1973
| month = January
| pmid = 4685905
}}</ref><ref>{{Cite journal
| author = [[Charlotte Burup Kristensen]], [[Jan Skov Jensen]], [[Peter Sogaard]], [[Helle Gervig Carstensen]] & [[Rasmus Mogelvang]]
| title = Atrial fibrillation in aortic stenosis--echocardiographic assessment and prognostic importance
| journal = [[Cardiovascular ultrasound]]
| volume = 10
| pages = 38
| year = 2012
| month = September
| doi = 10.1186/1476-7120-10-38
| pmid = 23006976
}}</ref><ref>{{Cite journal
| author = [[R. R. Wolfe]], [[D. J. Driscoll]], [[W. M. Gersony]], [[C. J. Hayes]], [[J. F. Keane]], [[L. Kidd]], [[W. M. O'Fallon]], [[D. R. Pieroni]] & [[W. H. Weidman]]
| title = Arrhythmias in patients with valvar aortic stenosis, valvar pulmonary stenosis, and ventricular septal defect. Results of 24-hour ECG monitoring
| journal = [[Circulation]]
| volume = 87
| issue = 2 Suppl
| pages = I89–101
| year = 1993
| month = February
| pmid = 8425327
}}</ref><ref name="pmid23625304">{{cite journal| author=| title=Abstracts of the 36th Annual Meeting of the Society of General Internal Medicine. April 24-27, 2013. Denver, Colorado, USA. | journal=J Gen Intern Med | year= 2013 | volume= 28 Suppl 1 | issue=  | pages= S1-489 | pmid=23625304 | doi=10.1007/s11606-013-2436-y | pmc=3654146 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23625304  }} </ref><ref name="pmid12878741">{{cite journal| author=Vincentelli A, Susen S, Le Tourneau T, Six I, Fabre O, Juthier F et al.| title=Acquired von Willebrand syndrome in aortic stenosis. | journal=N Engl J Med | year= 2003 | volume= 349 | issue= 4 | pages= 343-9 | pmid=12878741 | doi=10.1056/NEJMoa022831 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12878741  }} </ref>
*[[Congestive heart failure]], particularly left-sided [[heart failure]] or [[systolic dysfunction]]<ref name="pmid17662495">{{cite journal| author=Antonini-Canterin F, Popescu BA, Popescu AC, Beladan CC, Korcova R, Piazza R et al.| title=Heart failure in patients with aortic stenosis: clinical and prognostic significance of carbohydrate antigen 125 and brain natriuretic peptide measurement. | journal=Int J Cardiol | year= 2008 | volume= 128 | issue= 3 | pages= 406-12 | pmid=17662495 | doi=10.1016/j.ijcard.2007.05.039 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17662495  }} </ref><ref>{{Cite journal
| author = [[C. M. Otto]], [[I. G. Burwash]], [[M. E. Legget]], [[B. I. Munt]], [[M. Fujioka]], [[N. L. Healy]], [[C. D. Kraft]], [[C. Y. Miyake-Hull]] & [[R. G. Schwaegler]]
| title = Prospective study of asymptomatic valvular aortic stenosis. Clinical, echocardiographic, and exercise predictors of outcome
| journal = [[Circulation]]
| volume = 95
| issue = 9
| pages = 2262–2270
| year = 1997
| month = May
| pmid = 9142003
}}</ref><ref name="pmid27753861">{{cite journal| author=Kim YJ| title=BR 02-1 MANAGEMENT OF HYPERTENSION IN SEVERE AORTIC STENOSIS. | journal=J Hypertens | year= 2016 | volume= 34 Suppl 1 - ISH 2016 Abstract Book | issue=  | pages= e30 | pmid=27753861 | doi=10.1097/01.hjh.0000499936.94867.5f | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27753861  }} </ref><ref>{{Cite journal
| author = [[W. M. Gersony]], [[C. J. Hayes]], [[D. J. Driscoll]], [[J. F. Keane]], [[L. Kidd]], [[W. M. O'Fallon]], [[D. R. Pieroni]], [[R. R. Wolfe]] & [[W. H. Weidman]]
| title = Bacterial endocarditis in patients with aortic stenosis, pulmonary stenosis, or ventricular septal defect
| journal = [[Circulation]]
| volume = 87
| issue = 2 Suppl
| pages = I121–I126
| year = 1993
| month = February
| pmid = 8425318
}}</ref><ref name="pmid15166752">{{cite journal| author=Taneja I, Marney A, Robertson D| title=Aortic stenosis and autonomic dysfunction: co-conspirators in syncope. | journal=Am J Med Sci | year= 2004 | volume= 327 | issue= 5 | pages= 281-3 | pmid=15166752 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15166752  }} </ref><ref>{{Cite journal
| author = [[S. Frank]], [[A. Johnson]] & [[J. Jr Ross]]
| title = Natural history of valvular aortic stenosis
| journal = [[British heart journal]]
| volume = 35
| issue = 1
| pages = 41–46
| year = 1973
| month = January
| pmid = 4685905
}}</ref>
*[[Left ventricular hypertrophy]]<ref>{{Cite journal
| author = [[Markku Kupari]], [[Heikki Turto]] & [[Jyri Lommi]]
| title = Left ventricular hypertrophy in aortic valve stenosis: preventive or promotive of systolic dysfunction and heart failure?
| journal = [[European heart journal]]
| volume = 26
| issue = 17
| pages = 1790–1796
| year = 2005
| month = September
| doi = 10.1093/eurheartj/ehi290
| pmid = 15860517
}}</ref><ref>{{Cite journal
| author = [[Markku Kupari]], [[Heikki Turto]] & [[Jyri Lommi]]
| title = Left ventricular hypertrophy in aortic valve stenosis: preventive or promotive of systolic dysfunction and heart failure?
| journal = [[European heart journal]]
| volume = 26
| issue = 17
| pages = 1790–1796
| year = 2005
| month = September
| doi = 10.1093/eurheartj/ehi290
| pmid = 15860517
}}</ref><ref name="pmid24065303">{{cite journal| author=Zasada W, Chyrchel M, Bobrowska B, Dudek D| title=Non-ST elevation myocardial infarction in a patient with severe degenerative aortic stenosis. | journal=Kardiol Pol | year= 2013 | volume= 71 | issue= 9 | pages= 986-7 | pmid=24065303 | doi=10.5603/KP.2013.0239 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24065303  }} </ref><ref>{{Cite journal
| author = [[C. M. Otto]], [[I. G. Burwash]], [[M. E. Legget]], [[B. I. Munt]], [[M. Fujioka]], [[N. L. Healy]], [[C. D. Kraft]], [[C. Y. Miyake-Hull]] & [[R. G. Schwaegler]]
| title = Prospective study of asymptomatic valvular aortic stenosis. Clinical, echocardiographic, and exercise predictors of outcome
| journal = [[Circulation]]
| volume = 95
| issue = 9
| pages = 2262–2270
| year = 1997
| month = May
| pmid = 9142003
}}</ref>


Additional complications of untreated aortic stenosis include:
*[[Angina]]
*[[Arrhythmias]]
*[[Arrhythmias]]
**[[Atrial fibrillation]]
**[[Ventricular arrhythmia]]s
*[[Bleeding]]: Impaired platelet function and coagulation abnormalities, as decreased levels of [[Von Willebrand factor]], can be seen in most patients with severe AS. This resolves after valve replacement procedure. 20% of patients have clinical bleeding, most often [[epistaxis]] or [[ecchymoses]]. [[Aortic stenosis]] may result in a form of [[von Willebrand disease]] due to an increased turbulence around the stenosed [[aortic valve]] which subsequently triggers a break down of [[coagulation]] [[factor VIII]]-associated antigen, (also called [[von Willebrand factor]]) and results in a variant of [[von Willebrand disease]].
*[[Hypertension]]
*[[Endocarditis]]
*[[Endocarditis]]
*Left-sided [[heart failure]] or [[systolic dysfunction]]
*[[Fainting]] or [[syncope]]: Since the stenosed aortic valve may limit the heart's output, people with aortic stenosis are at risk of [[syncope]] and dangerously low blood pressure with the use of some common medications. Ironically, these same medicines are used to treat a variety of cardiovascular diseases, many of which may co-exist with aortic stenosis. Examples include [[nitroglycerin]], [[nitrates]], [[ACE inhibitor]]s, [[terazosin]] (Hytrin), and [[hydralazine]]. Note that all of these substances lead to peripheral [[vasodilation]]. Normally, however, in the absence of aortic stenosis, the heart is able to increase its output and thereby offset the effect of the dilated blood vessels. However, some cases of aortic stenosis can be associated with outflow blood obstruction which can prevent an increase of the [[cardiac output]]. Hence, low [[blood pressure]] or [[syncope]] may ensue.
*[[Left ventricular hypertrophy]]
*[[Left ventricular hypertrophy]]
*[[Atrial fibrillation]]
*[[Myocardial infarction]]
*[[Myocardial infarction]]
*[[Angina]]
*[[Fainting]] or [[syncope]]
* Impaired platelet function and coagulation abnormalities as decreased levels of [[Von Willebrand factor]] can be seen in most patients with severe AS. This resolves after valve replacement procedure. 20% of patients have clinical bleeding, most often [[epistaxis]] or [[ecchymoses]] <ref name="pmid12878741">{{cite journal| author=Vincentelli A, Susen S, Le Tourneau T, Six I, Fabre O, Juthier F et al.| title=Acquired von Willebrand syndrome in aortic stenosis. | journal=N Engl J Med | year= 2003 | volume= 349 | issue= 4 | pages= 343-9 | pmid=12878741 | doi=10.1056/NEJMoa022831 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12878741  }} </ref>


====Bicuspid Aortic Valve Disease====
Bicuspid aortic valve disease is associated with the following complications:<ref name="pmid835475">{{cite journal |author=Fenoglio JJ, McAllister HA, DeCastro CM, Davia JE, Cheitlin MD |title=Congenital bicuspid aortic valve after age 20 |journal=[[The American Journal of Cardiology]] |volume=39 |issue=2 |pages=164–9 |year=1977 |month=February |pmid=835475 |doi= |url= |accessdate=2012-04-10}}</ref><ref name="pmid15723989">{{cite journal |author=Lewin MB, Otto CM |title=The bicuspid aortic valve: adverse outcomes from infancy to old age |journal=[[Circulation]] |volume=111 |issue=7 |pages=832–4 |year=2005 |month=February |pmid=15723989 |doi=10.1161/01.CIR.0000157137.59691.0B |url=http://circ.ahajournals.org/cgi/pmidlookup?view=long&pmid=15723989 |accessdate=2012-04-10}}</ref><ref name="pmid11082359">{{cite journal |author=Keane MG, Wiegers SE, Plappert T, Pochettino A, Bavaria JE, Sutton MG |title=Bicuspid aortic valves are associated with aortic dilatation out of proportion to coexistent valvular lesions |journal=[[Circulation]] |volume=102 |issue=19 Suppl 3 |pages=III35–9 |year=2000 |month=November |pmid=11082359 |doi= |url=http://circ.ahajournals.org/cgi/pmidlookup?view=long&pmid=11082359 |accessdate=2012-04-10}}</ref><ref name="pmid7468467">{{cite journal |author=Roberts WC, Morrow AG, McIntosh CL, Jones M, Epstein SE |title=Congenitally bicuspid aortic valve causing severe, pure aortic regurgitation without superimposed infective endocarditis. Analysis of 13 patients requiring aortic valve replacement |journal=[[The American Journal of Cardiology]] |volume=47 |issue=2 |pages=206–9 |year=1981 |month=February |pmid=7468467 |doi= |url= |accessdate=2012-04-10}}</ref><ref name="pmid8425318">{{cite journal |author=Gersony WM, Hayes CJ, Driscoll DJ, Keane JF, Kidd L, O'Fallon WM, Pieroni DR, Wolfe RR, Weidman WH |title=Bacterial endocarditis in patients with aortic stenosis, pulmonary stenosis, or ventricular septal defect |journal=[[Circulation]] |volume=87 |issue=2 Suppl |pages=I121–6 |year=1993 |month=February |pmid=8425318 |doi= |url= |accessdate=2012-04-10}}</ref><ref name="pmid8425319">{{cite journal |author=Keane JF, Driscoll DJ, Gersony WM, Hayes CJ, Kidd L, O'Fallon WM, Pieroni DR, Wolfe RR, Weidman WH |title=Second natural history study of congenital heart defects. Results of treatment of patients with aortic valvar stenosis |journal=[[Circulation]] |volume=87 |issue=2 Suppl |pages=I16–27 |year=1993 |month=February |pmid=8425319 |doi= |url= |accessdate=2012-04-10}}</ref>
*[[Aortic stenosis]] in the majority of patients (75%)
*[[Aortic insufficiency]]
*[[Endocarditis]]
*[[Aortic aneurysm]]
*[[Aortic dissection]]
*[[Sudden death]] can occur in children during and immediately after exertion especially among those with pressure gradient > 50 mm Hg across the aortic valve


Since the stenosed aortic valve may limit the heart's output, people with aortic stenosis are at risk of [[syncope]] and dangerously low blood pressure should they use any of a number of common medications. Ironically, these same medicines are used to treat a variety of cardiovascular diseases, many of which may co-exist with aortic stenosis. Examples include [[nitroglycerin]], [[nitrates]], [[ACE inhibitor]]s, [[terazosin]] (Hytrin), and [[hydralazine]]. Note that all of these substances lead to peripheral [[vasodilation]]. Normally, however, in the absence of aortic stenosis, the heart is able to increase its output and thereby offset the effect of the dilated blood vessels. In some cases of aortic stenosis, however, due to the obstruction of blood flow out of the heart caused by the stenosed aortic valve, [[cardiac output]] cannot be increased. Low blood pressure or [[syncope]] may ensue.
===Prognosis===
====Asymptomatic Patients====
*The [[prognosis]] of patients with aortic stenosis who do not have [[symptoms]] is quite good. The annual [[mortality rate]] is < 1% per year in [[asymptomatic]] patients.ref>Lancellotti P, Magne J, Donal E, et al. Clinical outcome in asymptomatic severe aortic stenosis insights from the new proposed aortic stenosis grading classification. J Am Coll Cardiol. Jan 17 2012;59(3):235-43.</ref>
*Only 4% of [[sudden cardiac death]]s that occur in patients with aortic stenosis occur in those patients who are [[asymptomatic]].


==Prognosis==
====Symptomatic Patients====
Left untreated, the average survival is 5 years after the onset of angina, 3 years after the onset of syncope, and 1 year after the onset of congestive heart failure <ref name="pmid4894151">{{cite journal| author=Ross J, Braunwald E| title=Aortic stenosis. | journal=Circulation | year= 1968 | volume= 38 | issue= 1 Suppl | pages= 61-7 | pmid=4894151 | doi= | pmc= | url= }} </ref><ref name="pmid3337000">{{cite journal| author=Kelly TA, Rothbart RM, Cooper CM, Kaiser DL, Smucker ML, Gibson RS| title=Comparison of outcome of asymptomatic to symptomatic patients older than 20 years of age with valvular aortic stenosis. | journal=Am J Cardiol | year= 1988 | volume= 61 | issue= 1 | pages= 123-30 | pmid=3337000 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3337000  }} </ref><ref name="pmid8712130">{{cite journal| author=Iivanainen AM, Lindroos M, Tilvis R, Heikkilä J, Kupari M| title=Natural history of aortic valve stenosis of varying severity in the elderly. | journal=Am J Cardiol | year= 1996 | volume= 78 | issue= 1 | pages= 97-101 | pmid=8712130 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8712130  }} </ref>.  There is also a high risk of [[sudden cardiac death]], which may occur without any prior symptoms <ref name="pmid4894151">{{cite journal| author=Ross J, Braunwald E| title=Aortic stenosis. | journal=Circulation | year= 1968 | volume= 38 | issue= 1 Suppl | pages= 61-7 | pmid=4894151 | doi= | pmc= | url= }} </ref>. Sudden death occurs in less than 1% of patients per year when patients with aortic stenosis are followed prospectively <ref name="pmid7189084">{{cite journal| author=Chizner MA, Pearle DL, deLeon AC| title=The natural history of aortic stenosis in adults. | journal=Am Heart J | year= 1980 | volume= 99 | issue= 4 | pages= 419-24 | pmid=7189084 | doi= | pmc= | url= }} </ref>.
*Medical treatment of newly diagnosed moderate to severe [[symptomatic]] aortic stenosis is associated with a 25% [[mortality]] at one year and a 50% mortality at two years. Half of the deaths are due to [[sudden cardiac death]].<ref name="pmid4894151">{{cite journal| author=Ross J, Braunwald E| title=Aortic stenosis. | journal=Circulation | year= 1968 | volume= 38 | issue= 1 Suppl | pages= 61-7 | pmid=4894151 | doi= | pmc= | url= }} </ref><ref name="pmid7189084">{{cite journal| author=Chizner MA, Pearle DL, deLeon AC| title=The natural history of aortic stenosis in adults. | journal=Am Heart J | year= 1980 | volume= 99 | issue= 4 | pages= 419-24 | pmid=7189084 | doi= | pmc= | url= }} </ref><ref name="pmid26140146">{{cite journal| author=Rashedi N, Otto CM| title=Aortic Stenosis: Changing Disease Concepts. | journal=J Cardiovasc Ultrasound | year= 2015 | volume= 23 | issue= 2 | pages= 59-69 | pmid=26140146 | doi=10.4250/jcu.2015.23.2.59 | pmc=4486179 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26140146  }} </ref>
*When aortic stenosis is left untreated, the average survival is 5 years after the onset of angina, 3 years after the onset of [[syncope]], and 1 year after the onset of [[congestive heart failure]].<ref name="pmid4894151">{{cite journal| author=Ross J, Braunwald E| title=Aortic stenosis. | journal=Circulation | year= 1968 | volume= 38 | issue= 1 Suppl | pages= 61-7 | pmid=4894151 | doi= | pmc= | url= }} </ref><ref name="pmid3337000">{{cite journal| author=Kelly TA, Rothbart RM, Cooper CM, Kaiser DL, Smucker ML, Gibson RS| title=Comparison of outcome of asymptomatic to symptomatic patients older than 20 years of age with valvular aortic stenosis. | journal=Am J Cardiol | year= 1988 | volume= 61 | issue= 1 | pages= 123-30 | pmid=3337000 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3337000  }} </ref><ref name="pmid8712130">{{cite journal| author=Iivanainen AM, Lindroos M, Tilvis R, Heikkilä J, Kupari M| title=Natural history of aortic valve stenosis of varying severity in the elderly. | journal=Am J Cardiol | year= 1996 | volume= 78 | issue= 1 | pages= 97-101 | pmid=8712130 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8712130  }} </ref>


==Low Flow Aortic Stenosis==
====Low Flow, Low Gradient Aortic Stenosis with Low Ejection Fraction====
If there is a decline in left ventricular function due to [[systolic dysfunction]], there may be only a moderate transvalvular gradient or low flow aortic stenosis.  If there is fibrosis of the [[left ventricle]], there may be incomplete recovery after aortic valve replacement. This scenario can also occur among patients in whom there is a history of [[myocardial infarction]]: there is insufficient contractility to mount an aortic gradient.
In low flow, low gradient, low [[ejection fraction]] aortic stenosis, the [[aortic valve area]] should increase to more than  1.2 cm<sup>2</sup> and the [[Intravascular pressure gradient|mean pressure gradient]] should rise above 30 mm Hg following infusion with [[dobutamine]]. While early surgical [[mortality]] is 32–33% in patients who fail to achieve these improvements with [[dobutamine]] infusions, it is only 5–7% in patients who demonstrate an increase in their [[contractility]] and gradient. Five years survival after [[surgery]] was 88% in patients with improved contractility and only 10–25% in patients with unimproved contractility after [[dobutamine]] infusion.<ref name="pmid12176952">{{cite journal| author=Nishimura RA, Grantham JA, Connolly HM, Schaff HV, Higano ST, Holmes DR| title=Low-output, low-gradient aortic stenosis in patients with depressed left ventricular systolic function: the clinical utility of the dobutamine challenge in the catheterization laboratory. | journal=Circulation | year= 2002 | volume= 106 | issue= 7 | pages= 809-13 | pmid=12176952 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12176952  }} </ref>
 
====Definition====
#An aortic valve areas < 1.0 cm2
#A left ventricular ejection fraction < 40%
#A mean pressure difference or gradient across the aortic valve of < 30 mm Hg
 
With a dobutamine infusion, the aortic valve area should increase to > 1.2 cm2, and the mean pressure gradient should rise above 30 mm Hg. If there is a failure to acheive these improvements, early surgical mortality is 32-33%, but it is only 5–7% in those patients who can augment their contractility and gradient. Survival at five years was 88% after surgery if the patient can augment their contractility, but only 10–25% if the patient cannot augment their contractility.  
 
It should be noted that left ventricular contractile reserve is a better predictor of surgical outcomes than  markers of stenosis. Aortic valve surgery is indicated if there is severe AS along with an increase in the systolic velocity integral by >20% during a dobutamine infusion.


==References==
==References==
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[[CME Category::Cardiology]]


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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editors-In-Chief: Mohammed A. Sbeih, M.D. [2]; Lakshmi Gopalakrishnan, M.B.B.S. [3]; Usama Talib, BSc, MD [4]

Overview

Left untreated, aortic valve stenosis can lead to angina, syncope, congestive heart failure, atrial fibrillation, endocarditis, and sudden cardiac death. Surgical treatment of aortic stenosis also carries risks and potential complications that include vascular complications and mitral valve injury. When aortic stenosis is left untreated, the average survival is 5 years after the onset of angina, 3 years after the onset of syncope, and 1 year after the onset of congestive heart failure.[1][2][3]

Natural History, Complications, and Prognosis

Natural History

Degenerative Calcific Aortic Stenosis

  • Aortic stenosis due to the degeneration of a calcified aortic valve has a prolonged latent period during which symptoms are minimal or even lacking. This form of aortic stenosis presents later in life, usually after the age of 75. [4][5]
  • Once moderate aortic stenosis is present and symptomatic, the average rate of progression of the valvular stenosis is a decrease in the valve area of 0.1 cm2 per year.[5][6]
  • In addition, there is an increase in the jet velocity of 0.3 m/second per year and an increase in the mean pressure gradient of 7 mm Hg per year.[7][8][9]
  • There is a tremendous individual variability in the rate of progression of aortic stenosis. Risk factors for atherosclerosis (such as age, smoking, hypertension, obesity and diabetes, lipid abnormalities, chronic renal failure and dialysis) and atherosclerotic disease itself (such as concomitant coronary artery disease) are associated with more rapid rates of progression of the severity of the aortic stenosis.[10]

Aortic Stenosis Due to Rheumatic Heart Disease

  • The aortic stenosis due to rheumatic heart disease is amongst the most common causes of aortic stenosis. It is calculated to be around 24% of the total prevalence.[11]

Bicuspid Aortic Valve Disease

  • Bicuspid aortic valve stenosis presents one or two decades earlier than the tricuspid aortic valve.
  • The rate of progression of degenerative aortic stenosis can be faster in patients with bicuspid aortic valve than in those with congenital or rheumatic disease.[12][13]
  • Bicuspid aortic valve functions without any significant pressure gradient during childhood. However, the thickening and calcification of the valves may be detectable pathologically and on echocardiography by the second decade.[14]
  • Approximately 75% of bicuspid aortic valves progress into aortic stenosis requiring operative correction.[15][16]
  • Bicuspid aortic stenosis progressively leads to heart failure, arrythmias, angina and other symptoms. These symptoms generally manifests between 40 to 60 years of age, which is relatively a younger age than that of the manifestation of the symptoms caused by aortic stenosis. However, children who develop early pathological changes in bicuspid aortic valve are more likely to develop aortic insufficiency than stenosis.[15]

Aortic Sclerosis

  • Aortic sclerosis (defined as aortic valve thickening without obstruction to ventricular outflow) may progress to narrowing of the aortic valve or aortic stenosis. The decrease in pulse pressure or upstroke of the pulse in a patient with aortic sclerosis is a sign of progression to aortic stenosis.[17]

Complications

Degenerative Calcific Aortic Stenosis

If left untreated, aortic stenosis may lead to complications such as angina, syncope, or heart failure. A complete list of complications of aortic stenosis includes the following:[18][19][20][21][22]

Bicuspid Aortic Valve Disease

Bicuspid aortic valve disease is associated with the following complications:[15][16][33][34][35][36]

Prognosis

Asymptomatic Patients

  • The prognosis of patients with aortic stenosis who do not have symptoms is quite good. The annual mortality rate is < 1% per year in asymptomatic patients.ref>Lancellotti P, Magne J, Donal E, et al. Clinical outcome in asymptomatic severe aortic stenosis insights from the new proposed aortic stenosis grading classification. J Am Coll Cardiol. Jan 17 2012;59(3):235-43.</ref>
  • Only 4% of sudden cardiac deaths that occur in patients with aortic stenosis occur in those patients who are asymptomatic.

Symptomatic Patients

Low Flow, Low Gradient Aortic Stenosis with Low Ejection Fraction

In low flow, low gradient, low ejection fraction aortic stenosis, the aortic valve area should increase to more than 1.2 cm2 and the mean pressure gradient should rise above 30 mm Hg following infusion with dobutamine. While early surgical mortality is 32–33% in patients who fail to achieve these improvements with dobutamine infusions, it is only 5–7% in patients who demonstrate an increase in their contractility and gradient. Five years survival after surgery was 88% in patients with improved contractility and only 10–25% in patients with unimproved contractility after dobutamine infusion.[39]

References

  1. ↑ 1.0 1.1 1.2 Ross J, Braunwald E (1968). "Aortic stenosis". Circulation. 38 (1 Suppl): 61–7. PMID 4894151.
  2. ↑ 2.0 2.1 Kelly TA, Rothbart RM, Cooper CM, Kaiser DL, Smucker ML, Gibson RS (1988). "Comparison of outcome of asymptomatic to symptomatic patients older than 20 years of age with valvular aortic stenosis". Am J Cardiol. 61 (1): 123–30. PMID 3337000.
  3. ↑ 3.0 3.1 Iivanainen AM, Lindroos M, Tilvis R, Heikkilä J, Kupari M (1996). "Natural history of aortic valve stenosis of varying severity in the elderly". Am J Cardiol. 78 (1): 97–101. PMID 8712130.
  4. ↑ Townsend CM, et al. Sabiston Textbook of Surgery. 18th ed. Saunders; 2008:1841-1844.
  5. ↑ 5.0 5.1 Faggiano P, Aurigemma GP, Rusconi C, Gaasch WH (1996). "Progression of valvular aortic stenosis in adults: literature review and clinical implications". Am Heart J. 132 (2 Pt 1): 408–17. PMID 8701905.
  6. ↑ Baumgartner H, Hung J, Bermejo J, Chambers JB, Evangelista A, Griffin BP; et al. (2009). "Echocardiographic assessment of valve stenosis: EAE/ASE recommendations for clinical practice". J Am Soc Echocardiogr. 22 (1): 1–23, quiz 101-2. doi:10.1016/j.echo.2008.11.029. PMID 19130998.
  7. ↑ Cheitlin MD, Gertz EW, Brundage BH, Carlson CJ, Quash JA, Bode RS (1979). "Rate of progression of severity of valvular aortic stenosis in the adult". Am Heart J. 98 (6): 689–700. PMID 495418.
  8. ↑ Jonasson R, Jonsson B, Nordlander R, Orinius E, Szamosi A (1983). "Rate of progression of severity of valvular aortic stenosis". Acta Med Scand. 213 (1): 51–4. PMID 6829320.
  9. ↑ Peter M, Hoffmann A, Parker C, Lüscher T, Burckhardt D (1993). "Progression of aortic stenosis. Role of age and concomitant coronary artery disease". Chest. 103 (6): 1715–9. PMID 8404089.
  10. ↑ Mohler ER, Sheridan MJ, Nichols R, Harvey WP, Waller BF (1991). "Development and progression of aortic valve stenosis: atherosclerosis risk factors--a causal relationship? A clinical morphologic study". Clin Cardiol. 14 (12): 995–9. PMID 1841025.
  11. ↑ Passik CS, Ackermann DM, Pluth JR, Edwards WD (1987). "Temporal changes in the causes of aortic stenosis: a surgical pathologic study of 646 cases". Mayo Clin Proc. 62 (2): 119–23. PMID 3807436.
  12. ↑ Kamath AR, Pai RG (2008). "Risk factors for progression of calcific aortic stenosis and potential therapeutic targets". Int J Angiol. 17 (2): 63–70. PMC 2728414. PMID 22477390.
  13. ↑ Rosenhek R, Binder T, Porenta G, Lang I, Christ G, Schemper M; et al. (2000). "Predictors of outcome in severe, asymptomatic aortic stenosis". N Engl J Med. 343 (9): 611–7. doi:10.1056/NEJM200008313430903. PMID 10965007.
  14. ↑ Beppu S, Suzuki S, Matsuda H, Ohmori F, Nagata S, Miyatake K (1993). "Rapidity of progression of aortic stenosis in patients with congenital bicuspid aortic valves". The American Journal of Cardiology. 71 (4): 322–7. PMID 8427176. Unknown parameter |month= ignored (help); |access-date= requires |url= (help)
  15. ↑ 15.0 15.1 15.2 Fenoglio JJ, McAllister HA, DeCastro CM, Davia JE, Cheitlin MD (1977). "Congenital bicuspid aortic valve after age 20". The American Journal of Cardiology. 39 (2): 164–9. PMID 835475. Unknown parameter |month= ignored (help); |access-date= requires |url= (help)
  16. ↑ 16.0 16.1 Lewin MB, Otto CM (2005). "The bicuspid aortic valve: adverse outcomes from infancy to old age". Circulation. 111 (7): 832–4. doi:10.1161/01.CIR.0000157137.59691.0B. PMID 15723989. Retrieved 2012-04-10. Unknown parameter |month= ignored (help)
  17. ↑ Di Minno MN, Di Minno A, Songia P, Ambrosino P, Gripari P, Ravani A; et al. (2016). "Markers of subclinical atherosclerosis in patients with aortic valve sclerosis: A meta-analysis of literature studies". Int J Cardiol. 223: 364–370. doi:10.1016/j.ijcard.2016.08.122. PMID 27543711.
  18. ↑ S. Frank, A. Johnson & J. Jr Ross (1973). "Natural history of valvular aortic stenosis". British heart journal. 35 (1): 41–46. PMID 4685905. Unknown parameter |month= ignored (help)
  19. ↑ Charlotte Burup Kristensen, Jan Skov Jensen, Peter Sogaard, Helle Gervig Carstensen & Rasmus Mogelvang (2012). "Atrial fibrillation in aortic stenosis--echocardiographic assessment and prognostic importance". Cardiovascular ultrasound. 10: 38. doi:10.1186/1476-7120-10-38. PMID 23006976. Unknown parameter |month= ignored (help)
  20. ↑ R. R. Wolfe, D. J. Driscoll, W. M. Gersony, C. J. Hayes, J. F. Keane, L. Kidd, W. M. O'Fallon, D. R. Pieroni & W. H. Weidman (1993). "Arrhythmias in patients with valvar aortic stenosis, valvar pulmonary stenosis, and ventricular septal defect. Results of 24-hour ECG monitoring". Circulation. 87 (2 Suppl): I89–101. PMID 8425327. Unknown parameter |month= ignored (help)
  21. ↑ "Abstracts of the 36th Annual Meeting of the Society of General Internal Medicine. April 24-27, 2013. Denver, Colorado, USA". J Gen Intern Med. 28 Suppl 1: S1–489. 2013. doi:10.1007/s11606-013-2436-y. PMC 3654146. PMID 23625304.
  22. ↑ Vincentelli A, Susen S, Le Tourneau T, Six I, Fabre O, Juthier F; et al. (2003). "Acquired von Willebrand syndrome in aortic stenosis". N Engl J Med. 349 (4): 343–9. doi:10.1056/NEJMoa022831. PMID 12878741.
  23. ↑ Antonini-Canterin F, Popescu BA, Popescu AC, Beladan CC, Korcova R, Piazza R; et al. (2008). "Heart failure in patients with aortic stenosis: clinical and prognostic significance of carbohydrate antigen 125 and brain natriuretic peptide measurement". Int J Cardiol. 128 (3): 406–12. doi:10.1016/j.ijcard.2007.05.039. PMID 17662495.
  24. ↑ C. M. Otto, I. G. Burwash, M. E. Legget, B. I. Munt, M. Fujioka, N. L. Healy, C. D. Kraft, C. Y. Miyake-Hull & R. G. Schwaegler (1997). "Prospective study of asymptomatic valvular aortic stenosis. Clinical, echocardiographic, and exercise predictors of outcome". Circulation. 95 (9): 2262–2270. PMID 9142003. Unknown parameter |month= ignored (help)
  25. ↑ Kim YJ (2016). "BR 02-1 MANAGEMENT OF HYPERTENSION IN SEVERE AORTIC STENOSIS". J Hypertens. 34 Suppl 1 - ISH 2016 Abstract Book: e30. doi:10.1097/01.hjh.0000499936.94867.5f. PMID 27753861.
  26. ↑ W. M. Gersony, C. J. Hayes, D. J. Driscoll, J. F. Keane, L. Kidd, W. M. O'Fallon, D. R. Pieroni, R. R. Wolfe & W. H. Weidman (1993). "Bacterial endocarditis in patients with aortic stenosis, pulmonary stenosis, or ventricular septal defect". Circulation. 87 (2 Suppl): I121–I126. PMID 8425318. Unknown parameter |month= ignored (help)
  27. ↑ Taneja I, Marney A, Robertson D (2004). "Aortic stenosis and autonomic dysfunction: co-conspirators in syncope". Am J Med Sci. 327 (5): 281–3. PMID 15166752.
  28. ↑ S. Frank, A. Johnson & J. Jr Ross (1973). "Natural history of valvular aortic stenosis". British heart journal. 35 (1): 41–46. PMID 4685905. Unknown parameter |month= ignored (help)
  29. ↑ Markku Kupari, Heikki Turto & Jyri Lommi (2005). "Left ventricular hypertrophy in aortic valve stenosis: preventive or promotive of systolic dysfunction and heart failure?". European heart journal. 26 (17): 1790–1796. doi:10.1093/eurheartj/ehi290. PMID 15860517. Unknown parameter |month= ignored (help)
  30. ↑ Markku Kupari, Heikki Turto & Jyri Lommi (2005). "Left ventricular hypertrophy in aortic valve stenosis: preventive or promotive of systolic dysfunction and heart failure?". European heart journal. 26 (17): 1790–1796. doi:10.1093/eurheartj/ehi290. PMID 15860517. Unknown parameter |month= ignored (help)
  31. ↑ Zasada W, Chyrchel M, Bobrowska B, Dudek D (2013). "Non-ST elevation myocardial infarction in a patient with severe degenerative aortic stenosis". Kardiol Pol. 71 (9): 986–7. doi:10.5603/KP.2013.0239. PMID 24065303.
  32. ↑ C. M. Otto, I. G. Burwash, M. E. Legget, B. I. Munt, M. Fujioka, N. L. Healy, C. D. Kraft, C. Y. Miyake-Hull & R. G. Schwaegler (1997). "Prospective study of asymptomatic valvular aortic stenosis. Clinical, echocardiographic, and exercise predictors of outcome". Circulation. 95 (9): 2262–2270. PMID 9142003. Unknown parameter |month= ignored (help)
  33. ↑ Keane MG, Wiegers SE, Plappert T, Pochettino A, Bavaria JE, Sutton MG (2000). "Bicuspid aortic valves are associated with aortic dilatation out of proportion to coexistent valvular lesions". Circulation. 102 (19 Suppl 3): III35–9. PMID 11082359. Retrieved 2012-04-10. Unknown parameter |month= ignored (help)
  34. ↑ Roberts WC, Morrow AG, McIntosh CL, Jones M, Epstein SE (1981). "Congenitally bicuspid aortic valve causing severe, pure aortic regurgitation without superimposed infective endocarditis. Analysis of 13 patients requiring aortic valve replacement". The American Journal of Cardiology. 47 (2): 206–9. PMID 7468467. Unknown parameter |month= ignored (help); |access-date= requires |url= (help)
  35. ↑ Gersony WM, Hayes CJ, Driscoll DJ, Keane JF, Kidd L, O'Fallon WM, Pieroni DR, Wolfe RR, Weidman WH (1993). "Bacterial endocarditis in patients with aortic stenosis, pulmonary stenosis, or ventricular septal defect". Circulation. 87 (2 Suppl): I121–6. PMID 8425318. Unknown parameter |month= ignored (help); |access-date= requires |url= (help)
  36. ↑ Keane JF, Driscoll DJ, Gersony WM, Hayes CJ, Kidd L, O'Fallon WM, Pieroni DR, Wolfe RR, Weidman WH (1993). "Second natural history study of congenital heart defects. Results of treatment of patients with aortic valvar stenosis". Circulation. 87 (2 Suppl): I16–27. PMID 8425319. Unknown parameter |month= ignored (help); |access-date= requires |url= (help)
  37. ↑ Chizner MA, Pearle DL, deLeon AC (1980). "The natural history of aortic stenosis in adults". Am Heart J. 99 (4): 419–24. PMID 7189084.
  38. ↑ Rashedi N, Otto CM (2015). "Aortic Stenosis: Changing Disease Concepts". J Cardiovasc Ultrasound. 23 (2): 59–69. doi:10.4250/jcu.2015.23.2.59. PMC 4486179. PMID 26140146.
  39. ↑ Nishimura RA, Grantham JA, Connolly HM, Schaff HV, Higano ST, Holmes DR (2002). "Low-output, low-gradient aortic stenosis in patients with depressed left ventricular systolic function: the clinical utility of the dobutamine challenge in the catheterization laboratory". Circulation. 106 (7): 809–13. PMID 12176952.

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