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{{Aortic stenosis}}
{{Aortic stenosis}}
{{CMG}}; {{AOEIC}} [[User:Mohammed Sbeih|Mohammed A. Sbeih, M.D.]] [mailto:msbeih@wikidoc.org]; {{CZ}}; {{USAMA}} '''Assistant Editor-In-Chief:''' [[Kristin Feeney|Kristin Feeney, B.S.]] [mailto:kfeeney@elon.edu]; {{Rim}}
{{CMG}}; {{AOEIC}} {{Sara.Zand}} [[User:Mohammed Sbeih|Mohammed A. Sbeih, M.D.]] [mailto:msbeih@wikidoc.org]; {{CZ}}; {{USAMA}} '''Assistant Editor-In-Chief:''' [[Kristin Feeney|Kristin Feeney, B.S.]] [mailto:kfeeney@elon.edu]; {{Rim}}
 
{{SK}} AS; Aortic stenosis; AVR; Aortic valve replacement; TAVI; Transcatheter aortic valve implantation; ACEI; Angiotensin-converting enzyme inhibitor; CAD; Coronary artery disease; LV; Left ventricle
==Overview==
==Overview==
While medical therapy may improve the symptoms of patients with aortic stenosis (AS), medical therapy does not prolong life expectancy.  [[Aortic valve replacement]] (AVR) remains the definitive treatment of symptomatic aortic stenosis and it improves both the symptoms and life expectancy of patients with aortic stenosis. When pharmacological therapies are used, extreme caution must be taken in the administration of [[vasodilator]]s as excess vasodilation may lead to [[hypotension]], a reduction in perfusion pressure to the heart, a further decline in [[cardiac output]] and further [[hypotension]]. This downward spiral can be fatal and must be avoided at all costs.<ref name="pmid19038677">{{cite journal| author=Warnes CA, Williams RG, Bashore TM, Child JS, Connolly HM, Dearani JA et al.| title=ACC/AHA 2008 guidelines for the management of adults with congenital heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Develop Guidelines on the Management of Adults With Congenital Heart Disease). Developed in Collaboration With the American Society of Echocardiography, Heart Rhythm Society, International Society for Adult Congenital Heart Disease, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. | journal=J Am Coll Cardiol | year= 2008 | volume= 52 | issue= 23 | pages= e1-121 | pmid=19038677 | doi=10.1016/j.jacc.2008.10.001 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19038677  }} </ref><ref name="pmid16750677">{{cite journal| author=Otto CM| title=Valvular aortic stenosis: disease severity and timing of intervention. | journal=J Am Coll Cardiol | year= 2006 | volume= 47 | issue= 11 | pages= 2141-51 | pmid=16750677 | doi=10.1016/j.jacc.2006.03.002 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16750677  }} </ref>
Medical treatment of [[hypertension]] and [[hyperlipidemia]] according to the Guidelines is considered for [[patients]] with [[AS]]. Therapy with [[ACE inhibitor]] or [[ARB]]   may reduce the [[mortality rate]] in [[patients]] with [[AS]] who underwent [[TAVI]].


==Medical Therapy==
==Medical Therapy==
 
* [[Hypertension]] is common in [[patients]] with [[AS]], may be a risk factor for [[AS]], and increases the total [[pressure overload]] on the [[left ventricle]] in combination with [[valve]] obstruction.<ref name="pmid31290937">{{cite journal |vauthors=Nazarzadeh M, Pinho-Gomes AC, Smith Byrne K, Canoy D, Raimondi F, Ayala Solares JR, Otto CM, Rahimi K |title=Systolic Blood Pressure and Risk of Valvular Heart Disease: A Mendelian Randomization Study |journal=JAMA Cardiol |volume=4 |issue=8 |pages=788–795 |date=August 2019 |pmid=31290937 |pmc=6624812 |doi=10.1001/jamacardio.2019.2202 |url=}}</ref><ref name="pmid27486164">{{cite journal |vauthors=Nielsen OW, Sajadieh A, Sabbah M, Greve AM, Olsen MH, Boman K, Nienaber CA, Kesäniemi YA, Pedersen TR, Willenheimer R, Wachtell K |title=Assessing Optimal Blood Pressure in Patients With Asymptomatic Aortic Valve Stenosis: The Simvastatin Ezetimibe in Aortic Stenosis Study (SEAS) |journal=Circulation |volume=134 |issue=6 |pages=455–68 |date=August 2016 |pmid=27486164 |doi=10.1161/CIRCULATIONAHA.115.021213 |url=}}</ref><ref name="pmid16022957">{{cite journal |vauthors=Briand M, Dumesnil JG, Kadem L, Tongue AG, Rieu R, Garcia D, Pibarot P |title=Reduced systemic arterial compliance impacts significantly on left ventricular afterload and function in aortic stenosis: implications for diagnosis and treatment |journal=J Am Coll Cardiol |volume=46 |issue=2 |pages=291–8 |date=July 2005 |pmid=16022957 |doi=10.1016/j.jacc.2004.10.081 |url=}}</ref>
* [[Hypertension]] is common in [[patients]] with [[AS]], may be a risk factor for [[AS]], and increases the total [[pressure overload]] on the [[left ventricle]] in combination with [[valve]] obstruction.<ref name="pmid31290937">{{cite journal |vauthors=Nazarzadeh M, Pinho-Gomes AC, Smith Byrne K, Canoy D, Raimondi F, Ayala Solares JR, Otto CM, Rahimi K |title=Systolic Blood Pressure and Risk of Valvular Heart Disease: A Mendelian Randomization Study |journal=JAMA Cardiol |volume=4 |issue=8 |pages=788–795 |date=August 2019 |pmid=31290937 |pmc=6624812 |doi=10.1001/jamacardio.2019.2202 |url=}}</ref><ref name="pmid27486164">{{cite journal |vauthors=Nielsen OW, Sajadieh A, Sabbah M, Greve AM, Olsen MH, Boman K, Nienaber CA, Kesäniemi YA, Pedersen TR, Willenheimer R, Wachtell K |title=Assessing Optimal Blood Pressure in Patients With Asymptomatic Aortic Valve Stenosis: The Simvastatin Ezetimibe in Aortic Stenosis Study (SEAS) |journal=Circulation |volume=134 |issue=6 |pages=455–68 |date=August 2016 |pmid=27486164 |doi=10.1161/CIRCULATIONAHA.115.021213 |url=}}</ref>
* 2 small [[RCTs]] have not confirmed that [[antihypertensive]] [[ medications]] may reduce the [[cardiac output]] because [[AS]] does not result in fixed [[valve]] obstruction until late stage of the [[disease]].
* 2 small [[RCTs]] have not confirmed that [[antihypertensive]] [[ medications]] may reduce the [[cardiac output]] because [[AS]] does not result in fixed [[valve]] obstruction until late stage in the disease.
* The study of asymptomatic [[AS]] showed the association of [[hypertension]] with higher rate of [[ischemic cardiovascular]] events and a 2-fold higher [[mortality rate]] than  normotensive [[patients]] with [[AS]]. However, impact on progression of valve stenosis leading to [[symptoms]] requiring [[AVR]] was not observed.
* The study of asymptomatic [[AS]] showed the association of [[hypertension]] with higher rate of [[ischemic cardiovascular]] events and a 2-fold higher [[mortality rate]] ) than  normotensive [[patients]] with [[AS]]. However, impact on progression of valve stenosis leading to [[symptoms]] requiring [[AVR]] was not observed.
* [[Medical therapy]] for [[hypertension]] is based on the standard guidelines, initiating at a low dose and gradually titrated upward as needed to controlling of [[blood pressure]].
* [[Medical therapy]] for [[hypertension]] is based on the standard guidelines, initiating at a low dose and gradually titrated upward as needed to controlling of [[blood pressure]].
* There are no studies considering specific [[antihypertensive]] medications in [[patients]] with [[AS]], but [[diuretics]] may reduce [[stroke volume]], particularly if the [[LV]] chamber is small at baseline.  
* There are no studies considering specific [[antihypertensive]] medications in [[patients]] with [[AS]], but [[diuretics]] may reduce [[stroke volume]], particularly if the [[LV]] chamber is small at baseline.  
* The advantages of [[ACE inhibitors]] including beneficial effects on [[LV fibrosis]], control of [[hypertension]].  
* The advantages of [[ACE inhibitors]] include beneficial effects on [[LV fibrosis]], and control of [[hypertension]].<ref name="pmid15222408">{{cite journal |vauthors=O'Brien KD, Zhao XQ, Shavelle DM, Caulfield MT, Letterer RA, Kapadia SR, Probstfield JL, Otto CM |title=Hemodynamic effects of the angiotensin-converting enzyme inhibitor, ramipril, in patients with mild to moderate aortic stenosis and preserved left ventricular function |journal=J Investig Med |volume=52 |issue=3 |pages=185–91 |date=April 2004 |pmid=15222408 |doi=10.1136/jim-52-03-33 |url=}}</ref>
* Target [[blood pressure]]N should be considered higher for patients with [[AS]]  than is recommended for the general [[population]].
* Target [[blood pressure]] should be considered higher for [[patients]] with [[AS]]  than is recommended for the general [[population]].
*Concurrent [[coronary artery disease]] is common in [[patients]] with [[AS]],  and screening of all [[patients]] is recommended for [[hypercholesterolemia]], for primary and [[secondary prevention]] of [[CAD]].
*Concurrent [[coronary artery disease]] is common in [[patients]] with [[AS]],  and screening of all [[patients]] is recommended for [[hypercholesterolemia]], for primary and [[secondary prevention]] of [[CAD]].
* In [[RCTs]] of [[statin]] therapy for mild to [[moderate AS]], the rate of [[ischemic]] events was reduced by about 20% in the statin therapy group. Howerer, [[aortic valve]] event rates were not reduced.
* In [[RCTs]] of [[statin]] therapy for mild to [[moderate AS]], the rate of [[ischemic]] events was reduced by about 20% in the [[statin]] therapy group. Howerer, [[aortic valve]] event rates were not reduced.<ref name="pmid18765433">{{cite journal |vauthors=Rossebø AB, Pedersen TR, Boman K, Brudi P, Chambers JB, Egstrup K, Gerdts E, Gohlke-Bärwolf C, Holme I, Kesäniemi YA, Malbecq W, Nienaber CA, Ray S, Skjaerpe T, Wachtell K, Willenheimer R |title=Intensive lipid lowering with simvastatin and ezetimibe in aortic stenosis |journal=N Engl J Med |volume=359 |issue=13 |pages=1343–56 |date=September 2008 |pmid=18765433 |doi=10.1056/NEJMoa0804602 |url=}}</ref><ref name="pmid20048204">{{cite journal |vauthors=Chan KL, Teo K, Dumesnil JG, Ni A, Tam J |title=Effect of Lipid lowering with rosuvastatin on progression of aortic stenosis: results of the aortic stenosis progression observation: measuring effects of rosuvastatin (ASTRONOMER) trial |journal=Circulation |volume=121 |issue=2 |pages=306–14 |date=January 2010 |pmid=20048204 |doi=10.1161/CIRCULATIONAHA.109.900027 |url=}}</ref><ref name="pmid17276178">{{cite journal |vauthors=Moura LM, Ramos SF, Zamorano JL, Barros IM, Azevedo LF, Rocha-Gonçalves F, Rajamannan NM |title=Rosuvastatin affecting aortic valve endothelium to slow the progression of aortic stenosis |journal=J Am Coll Cardiol |volume=49 |issue=5 |pages=554–61 |date=February 2007 |pmid=17276178 |pmc=3951859 |doi=10.1016/j.jacc.2006.07.072 |url=}}</ref>
*In [[patients]] undergoing [[TAVI]], treatment  with [[renin–angiotensin system]] blocker therapy after the procedure had a lower 1-year [[mortality rate]] than those not treated with [[renin–angiotensin system blocker therapy]], with a relative risk reduction of about 20% to 50% and an [[absolute risk reduction]] between 2.4% and 5.0%.
*In [[patients]] undergoing [[TAVI]], treatment  with [[renin–angiotensin system]] blocker therapy after the procedure had a lower 1-year [[mortality rate]] than those not treated with [[renin–angiotensin system blocker therapy]], with a relative risk reduction of about 20% to 50% and an [[absolute risk reduction]] between 2.4% and 5.0%.
* Use of [[renin–angiotensin system inhibitor]], was associated with a lower 1-year [[mortality rate]] among [[patients]] with [[preserved LVEF]] but not among those with [[reduced LVEF]].
* Use of [[renin–angiotensin system inhibitor]], was associated with a lower 1-year [[mortality rate]] among [[patients]] with [[preserved LVEF]] but not among those with [[reduced LVEF]].<ref name="pmid28986405">{{cite journal |vauthors=Ochiai T, Saito S, Yamanaka F, Shishido K, Tanaka Y, Yamabe T, Shirai S, Tada N, Araki M, Naganuma T, Watanabe Y, Yamamoto M, Hayashida K |title=Renin-angiotensin system blockade therapy after transcatheter aortic valve implantation |journal=Heart |volume=104 |issue=8 |pages=644–651 |date=April 2018 |pmid=28986405 |doi=10.1136/heartjnl-2017-311738 |url=}}</ref><ref name="pmid28956773">{{cite journal |vauthors=Hansson NH, Sörensen J, Harms HJ, Kim WY, Nielsen R, Tolbod LP, Frøkiær J, Bouchelouche K, Dodt KK, Sihm I, Poulsen SH, Wiggers H |title=Metoprolol Reduces Hemodynamic and Metabolic Overload in Asymptomatic Aortic Valve Stenosis Patients: A Randomized Trial |journal=Circ Cardiovasc Imaging |volume=10 |issue=10 |pages= |date=October 2017 |pmid=28956773 |doi=10.1161/CIRCIMAGING.117.006557 |url=}}</ref><ref name="pmid30512100">{{cite journal |vauthors=Inohara T, Manandhar P, Kosinski AS, Matsouaka RA, Kohsaka S, Mentz RJ, Thourani VH, Carroll JD, Kirtane AJ, Bavaria JE, Cohen DJ, Kiefer TL, Gaca JG, Kapadia SR, Peterson ED, Vemulapalli S |title=Association of Renin-Angiotensin Inhibitor Treatment With Mortality and Heart Failure Readmission in Patients With Transcatheter Aortic Valve Replacement |journal=JAMA |volume=320 |issue=21 |pages=2231–2241 |date=December 2018 |pmid=30512100 |pmc=6583475 |doi=10.1001/jama.2018.18077 |url=}}</ref>
* 3 large well-designed [[RCTs]] failed to show a benefit of [[statins]]  for prevention of progression of [[AS]] in terms of [[hemodynamic severity]] or clinical outcomes.
* 3 large well-designed [[RCTs]] failed to show a benefit of [[statins]]  for prevention of progression of [[AS]] in terms of [[hemodynamic severity]] or clinical outcomes.
{| style="cellpadding=0; cellspacing= 0; width: 800px;"
|-
| style="padding: 0 5px; font-size: 100%; background: #4682B4; color: #FFFFFF;" align=center |'''Recommendations for medical therapy in aortic stenosis'''
|-
|style="font-size: 100; padding: 0 5px; background: #B8B8B8" align=left | '''  ([[ AHA guidelines classification scheme|Class I, Level of Evidence B]]):'''
|-
|style="padding: 0 5px; font-size: 100%; background: #F5F5F5; width: 70%" align=left|
❑ In [[patients]] at risk of developing [[AS]] (stage A) or asymptomatic [[AS]] (stage B,C), [[hypertension]] should be controlled by initiating low dose medications and titration doses based on [[clinical ]] evaluation<br>
|-
|style="font-size: 100; padding: 0 5px; background: #B8B8B8" align=left | '''  ([[ AHA guidelines classification scheme|Class I, Level of Evidence A]]):'''
|-
|style="padding: 0 5px; font-size: 100%; background: #F5F5F5; width: 70%" align=left|
❑[[Statin]] therapy is recommended in all [[patients]] with calcified [[AS]] for primary and [[secondary prevention]] of [[atherosclerosis]]
|-
|style="font-size: 100; padding: 0 5px; background: #B8B8B8" align=left | '''  ([[ AHA guidelines classification scheme|Class IIb, Level of Evidence B]]):'''
|-
|style="padding: 0 5px; font-size: 100%; background: #F5F5F5; width: 70%" align=left|
❑[[ACEI]] or [[ARB]] may be considered after [[TAVI]] to reduce the long term risk of [[all cause mortality]]
|-
|style="font-size: 100; padding: 0 5px; background: #B8B8B8" align=left | '''  NO benefit([[ AHA guidelines classification scheme|Class III, Level of Evidence A]]):'''
|-
|style="padding: 0 5px; font-size: 100%; background: #F5F5F5; width: 70%" align=left|
❑[[Statin]] is not indicated in [[calcified]] [[AS]] (stage B,C) for prevention of [[hemodynamic]] progression of [[AS]]
|}
{|
! colspan="2" style="background: PapayaWhip;" align="center" + |The above table adopted from 2020 AHA-ACC Guideline<ref name="pmid33332150">{{cite journal |vauthors=Otto CM, Nishimura RA, Bonow RO, Carabello BA, Erwin JP, Gentile F, Jneid H, Krieger EV, Mack M, McLeod C, O'Gara PT, Rigolin VH, Sundt TM, Thompson A, Toly C |title=2020 ACC/AHA Guideline for the Management of Patients With Valvular Heart Disease: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines |journal=Circulation |volume=143 |issue=5 |pages=e72–e227 |date=February 2021 |pmid=33332150 |doi=10.1161/CIR.0000000000000923 |url=}}</ref>
|-
|}
<span style="font-size:85%">'''Abbreviations:'''
'''[[AS]]:''' [[ Aortic stenosis]];
'''[[TAVI]]:''' [[Transcatheter aortic valve implantation]];
</span>
<br>


==References==
==References==

Latest revision as of 07:43, 26 July 2022
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-In-Chief: Sara Zand, M.D.[2] Mohammed A. Sbeih, M.D. [3]; Cafer Zorkun, M.D., Ph.D. [4]; Usama Talib, BSc, MD [5] Assistant Editor-In-Chief: Kristin Feeney, B.S. [6]; Rim Halaby, M.D. [7] Synonyms and keywords: AS; Aortic stenosis; AVR; Aortic valve replacement; TAVI; Transcatheter aortic valve implantation; ACEI; Angiotensin-converting enzyme inhibitor; CAD; Coronary artery disease; LV; Left ventricle

Overview

Medical treatment of hypertension and hyperlipidemia according to the Guidelines is considered for patients with AS. Therapy with ACE inhibitor or ARB may reduce the mortality rate in patients with AS who underwent TAVI.

Medical Therapy

Recommendations for medical therapy in aortic stenosis
(Class I, Level of Evidence B):

❑ In patients at risk of developing AS (stage A) or asymptomatic AS (stage B,C), hypertension should be controlled by initiating low dose medications and titration doses based on clinical evaluation

(Class I, Level of Evidence A):

❑Statin therapy is recommended in all patients with calcified AS for primary and secondary prevention of atherosclerosis

(Class IIb, Level of Evidence B):

❑ACEI or ARB may be considered after TAVI to reduce the long term risk of all cause mortality

NO benefit(Class III, Level of Evidence A):

❑Statin is not indicated in calcified AS (stage B,C) for prevention of hemodynamic progression of AS

The above table adopted from 2020 AHA-ACC Guideline[11]


Abbreviations: AS: Aortic stenosis; TAVI: Transcatheter aortic valve implantation;


References

  1. ↑ Nazarzadeh M, Pinho-Gomes AC, Smith Byrne K, Canoy D, Raimondi F, Ayala Solares JR, Otto CM, Rahimi K (August 2019). "Systolic Blood Pressure and Risk of Valvular Heart Disease: A Mendelian Randomization Study". JAMA Cardiol. 4 (8): 788–795. doi:10.1001/jamacardio.2019.2202. PMC 6624812 Check |pmc= value (help). PMID 31290937.
  2. ↑ Nielsen OW, Sajadieh A, Sabbah M, Greve AM, Olsen MH, Boman K, Nienaber CA, Kesäniemi YA, Pedersen TR, Willenheimer R, Wachtell K (August 2016). "Assessing Optimal Blood Pressure in Patients With Asymptomatic Aortic Valve Stenosis: The Simvastatin Ezetimibe in Aortic Stenosis Study (SEAS)". Circulation. 134 (6): 455–68. doi:10.1161/CIRCULATIONAHA.115.021213. PMID 27486164.
  3. ↑ Briand M, Dumesnil JG, Kadem L, Tongue AG, Rieu R, Garcia D, Pibarot P (July 2005). "Reduced systemic arterial compliance impacts significantly on left ventricular afterload and function in aortic stenosis: implications for diagnosis and treatment". J Am Coll Cardiol. 46 (2): 291–8. doi:10.1016/j.jacc.2004.10.081. PMID 16022957.
  4. ↑ O'Brien KD, Zhao XQ, Shavelle DM, Caulfield MT, Letterer RA, Kapadia SR, Probstfield JL, Otto CM (April 2004). "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. 52 (3): 185–91. doi:10.1136/jim-52-03-33. PMID 15222408.
  5. ↑ Rossebø AB, Pedersen TR, Boman K, Brudi P, Chambers JB, Egstrup K, Gerdts E, Gohlke-Bärwolf C, Holme I, Kesäniemi YA, Malbecq W, Nienaber CA, Ray S, Skjaerpe T, Wachtell K, Willenheimer R (September 2008). "Intensive lipid lowering with simvastatin and ezetimibe in aortic stenosis". N Engl J Med. 359 (13): 1343–56. doi:10.1056/NEJMoa0804602. PMID 18765433.
  6. ↑ Chan KL, Teo K, Dumesnil JG, Ni A, Tam J (January 2010). "Effect of Lipid lowering with rosuvastatin on progression of aortic stenosis: results of the aortic stenosis progression observation: measuring effects of rosuvastatin (ASTRONOMER) trial". Circulation. 121 (2): 306–14. doi:10.1161/CIRCULATIONAHA.109.900027. PMID 20048204.
  7. ↑ Moura LM, Ramos SF, Zamorano JL, Barros IM, Azevedo LF, Rocha-Gonçalves F, Rajamannan NM (February 2007). "Rosuvastatin affecting aortic valve endothelium to slow the progression of aortic stenosis". J Am Coll Cardiol. 49 (5): 554–61. doi:10.1016/j.jacc.2006.07.072. PMC 3951859. PMID 17276178.
  8. ↑ Ochiai T, Saito S, Yamanaka F, Shishido K, Tanaka Y, Yamabe T, Shirai S, Tada N, Araki M, Naganuma T, Watanabe Y, Yamamoto M, Hayashida K (April 2018). "Renin-angiotensin system blockade therapy after transcatheter aortic valve implantation". Heart. 104 (8): 644–651. doi:10.1136/heartjnl-2017-311738. PMID 28986405.
  9. ↑ Hansson NH, Sörensen J, Harms HJ, Kim WY, Nielsen R, Tolbod LP, Frøkiær J, Bouchelouche K, Dodt KK, Sihm I, Poulsen SH, Wiggers H (October 2017). "Metoprolol Reduces Hemodynamic and Metabolic Overload in Asymptomatic Aortic Valve Stenosis Patients: A Randomized Trial". Circ Cardiovasc Imaging. 10 (10). doi:10.1161/CIRCIMAGING.117.006557. PMID 28956773.
  10. ↑ Inohara T, Manandhar P, Kosinski AS, Matsouaka RA, Kohsaka S, Mentz RJ, Thourani VH, Carroll JD, Kirtane AJ, Bavaria JE, Cohen DJ, Kiefer TL, Gaca JG, Kapadia SR, Peterson ED, Vemulapalli S (December 2018). "Association of Renin-Angiotensin Inhibitor Treatment With Mortality and Heart Failure Readmission in Patients With Transcatheter Aortic Valve Replacement". JAMA. 320 (21): 2231–2241. doi:10.1001/jama.2018.18077. PMC 6583475 Check |pmc= value (help). PMID 30512100.
  11. ↑ Otto CM, Nishimura RA, Bonow RO, Carabello BA, Erwin JP, Gentile F, Jneid H, Krieger EV, Mack M, McLeod C, O'Gara PT, Rigolin VH, Sundt TM, Thompson A, Toly C (February 2021). "2020 ACC/AHA Guideline for the Management of Patients With Valvular Heart Disease: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines". Circulation. 143 (5): e72–e227. doi:10.1161/CIR.0000000000000923. PMID 33332150 Check |pmid= value (help).

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