Chronic aortic regurgitation medical therapy: Difference between revisions

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{{Aortic insufficiency}}
{{Aortic insufficiency}}
{{CMG}}; '''Associate Editor-in-Chief:''' {{CZ}}; [[Varun Kumar]], M.B.B.S.; [[Lakshmi Gopalakrishnan]], M.B.B.S.; [[User:Mohammed Sbeih|Mohammed A. Sbeih, M.D.]] [mailto:msbeih@wikidoc.org] [[User:Mohammed Salih|Mohammed Salih, M.D.]]
{{CMG}}; '''Associate Editor-in-Chief:''' {{CZ}}; [[Varun Kumar]], M.B.B.S.; [[Lakshmi Gopalakrishnan]], M.B.B.S.; [[User:Mohammed Sbeih|Mohammed A. Sbeih, M.D.]] [mailto:msbeih@wikidoc.org]; [[User:AroojNaz|Arooj Naz, M.B.B.S]]  


==Overview==
==Overview==
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Use of drugs other than [[vasodilators]], such as [[digoxin]], [[diuretics]], and other positive [[inotropic]] drugs for long term treatment have no supporting data. [[Beta blockers]] are relatively contraindicated since they decrease [[heart rate]] and prolong diastolic phase. There by increasing the back flow of [[blood]] from [[aorta]]. However, [[beta blockers]] can be considered in patients with [[bicuspid aortic valve]] with mild AR and [[aortic root]] diameter of more than 40mm.<ref name="pmid18820172">{{cite journal |author=Bonow RO, Carabello BA, Chatterjee K, de Leon AC, Faxon DP, Freed MD, Gaasch WH, Lytle BW, Nishimura RA, O'Gara PT, O'Rourke RA, Otto CM, Shah PM, Shanewise JS |title=2008 Focused update incorporated into the ACC/AHA 2006 guidelines 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 (Writing Committee to Revise the 1998 Guidelines for the Management of Patients With Valvular Heart Disease): endorsed by the Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons |journal=[[Circulation]] |volume=118 |issue=15 |pages=e523–661 |year=2008 |month=October |pmid=18820172 |doi=10.1161/CIRCULATIONAHA.108.190748 |url=http://circ.ahajournals.org/cgi/pmidlookup?view=long&pmid=18820172 |accessdate=2011-03-24}}</ref>
Use of drugs other than [[vasodilators]], such as [[digoxin]], [[diuretics]], and other positive [[inotropic]] drugs for long term treatment have no supporting data. [[Beta blockers]] are relatively contraindicated since they decrease [[heart rate]] and prolong diastolic phase. There by increasing the back flow of [[blood]] from [[aorta]]. However, [[beta blockers]] can be considered in patients with [[bicuspid aortic valve]] with mild AR and [[aortic root]] diameter of more than 40mm.<ref name="pmid18820172">{{cite journal |author=Bonow RO, Carabello BA, Chatterjee K, de Leon AC, Faxon DP, Freed MD, Gaasch WH, Lytle BW, Nishimura RA, O'Gara PT, O'Rourke RA, Otto CM, Shah PM, Shanewise JS |title=2008 Focused update incorporated into the ACC/AHA 2006 guidelines 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 (Writing Committee to Revise the 1998 Guidelines for the Management of Patients With Valvular Heart Disease): endorsed by the Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons |journal=[[Circulation]] |volume=118 |issue=15 |pages=e523–661 |year=2008 |month=October |pmid=18820172 |doi=10.1161/CIRCULATIONAHA.108.190748 |url=http://circ.ahajournals.org/cgi/pmidlookup?view=long&pmid=18820172 |accessdate=2011-03-24}}</ref>


==2014 AHA/ACC Guideline for the Management of Patients With Valvular Heart Diseases <ref>{{Cite web  | last =  | first =  | title = 2014 AHA/ACC Guideline for the Management of Patients With Valvular Heart Disease: Executive Summary | url = http://circ.ahajournals.org/content/early/2014/02/27/CIR.0000000000000029.full.pdf+html | publisher =  | date =  | accessdate = 4 March 2014 }}</ref>==
==2020 AHA/ACC Guideline for the Management of Patients With Valvular Heart Diseases <ref>{{Cite web  | last =  | first =  | title = 2014 AHA/ACC Guideline for the Management of Patients With Valvular Heart Disease: Executive Summary | url = http://circ.ahajournals.org/content/early/2014/02/27/CIR.0000000000000029.full.pdf+html | publisher =  | date =  | accessdate = 4 March 2014 }}</ref>==


{|class="wikitable"
{| class="wikitable"
|-
|-
| colspan="1" style="text-align:center; background:LightGreen"|[[ACC AHA guidelines classification scheme#Classification of Recommendations|Class I]]
| colspan="1" style="text-align:center; background:LightGreen" |[[ACC AHA guidelines classification scheme#Classification of Recommendations|Class I]]
|-
|-
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''1. '''Treatment of [[hypertension]] ([[systolic]] BP >140 mm Hg) is recommended in patients with chronic [[AR]] ([[AR stages|stages B and C]]), preferably with dihydropyridine [[calcium channel blockers]] or [[ACE inhibitors]]/angiotensin-receptor blockers ([[ARBs]]) ([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence:B]])''<nowiki>"</nowiki>
| bgcolor="LightGreen" |<nowiki>"</nowiki>'''1. '''Treatment of [[hypertension]] ([[systolic]] BP >140 mm Hg) is recommended in patients with chronic [[AR]] ([[AR stages|stages B and C]]), preferably with dihydropyridine [[calcium channel blockers]] or [[ACE inhibitors]]/angiotensin-receptor blockers ([[ARBs]]) ([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence:B]]). [[Severe AR]] with symptoms and or [[LV systolic dysfunction]] ([[AR C2|Stages C2]] and D)that have surgical risk, [[LVEF]] is reduced with [[ACE inhibitor|ACE inhibitors]], [[ARBs]], and/or [[Sacubitril and Valsartan|sacubitril/valsartan]]'<ref name="“2020">{{cite web|url=https://www.ahajournals.org/doi/10.1161/CIR.0000000000000923#d1e5782}}</ref>
|}
|}
{|class="wikitable"
{| class="wikitable"
|-
|-
| colspan="1" style="text-align:center; background:LemonChiffon"|[[ACC AHA guidelines classification scheme#Classification of Recommendations|Class IIa]]
| colspan="1" style="text-align:center; background:LemonChiffon" |[[ACC AHA guidelines classification scheme#Classification of Recommendations|Class IIa]]
|-
|-
| bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''1. '''Medical therapy with [[ACE inhibitors]]/[[ARBs]] and [[beta blockers]] is reasonable in patients with severe [[AR]] who have symptoms and/or [[LV dysfunction]] (stages C2 and D) when surgery is not performed because of comorbidities ([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: B]]) ''<nowiki>"</nowiki>
| bgcolor="LemonChiffon" |<nowiki>"</nowiki>'''1. '''Medical therapy with [[ACE inhibitors]]/[[ARBs]] and [[beta blockers]] is reasonable in patients with severe [[AR]] who have symptoms and/or [[LV dysfunction]] (stages C2 and D) when surgery is not performed because of comorbidities ([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: B]]) ''<nowiki>"</nowiki>''
|}
|}


==2008 Focused Update Incorporated into the 2006 ACC/AHA Guidelines for the Management of Patients with Valvular Heart Disease (DO NOT EDIT)<ref name="pmid18820172">{{cite journal |author=Bonow RO, Carabello BA, Chatterjee K, ''et al.'' |title=2008 Focused update incorporated into the ACC/AHA 2006 guidelines 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 (Writing Committee to Revise the 1998 Guidelines for the Management of Patients With Valvular Heart Disease): endorsed by the Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons |journal=Circulation |volume=118 |issue=15 |pages=e523–661 |year=2008 |month=October |pmid=18820172 |doi=10.1161/CIRCULATIONAHA.108.190748 |url=}}</ref>==
==2008 Focused Update Incorporated into the 2006 ACC/AHA Guidelines for the Management of Patients with Valvular Heart Disease (DO NOT EDIT)<ref name="pmid18820172">{{cite journal |author=Bonow RO, Carabello BA, Chatterjee K, ''et al.'' |title=2008 Focused update incorporated into the ACC/AHA 2006 guidelines 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 (Writing Committee to Revise the 1998 Guidelines for the Management of Patients With Valvular Heart Disease): endorsed by the Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons |journal=Circulation |volume=118 |issue=15 |pages=e523–661 |year=2008 |month=October |pmid=18820172 |doi=10.1161/CIRCULATIONAHA.108.190748 |url=}}</ref>==
===Vasodilator Therapy (DO NOT EDIT)<ref name="pmid18820172">{{cite journal |author=Bonow RO, Carabello BA, Chatterjee K, ''et al.'' |title=2008 Focused update incorporated into the ACC/AHA 2006 guidelines 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 (Writing Committee to Revise the 1998 Guidelines for the Management of Patients With Valvular Heart Disease): endorsed by the Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons |journal=Circulation |volume=118 |issue=15 |pages=e523–661 |year=2008 |month=October |pmid=18820172 |doi=10.1161/CIRCULATIONAHA.108.190748 |url=}}</ref>===
===Vasodilator Therapy (DO NOT EDIT)<ref name="pmid18820172">{{cite journal |author=Bonow RO, Carabello BA, Chatterjee K, ''et al.'' |title=2008 Focused update incorporated into the ACC/AHA 2006 guidelines 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 (Writing Committee to Revise the 1998 Guidelines for the Management of Patients With Valvular Heart Disease): endorsed by the Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons |journal=Circulation |volume=118 |issue=15 |pages=e523–661 |year=2008 |month=October |pmid=18820172 |doi=10.1161/CIRCULATIONAHA.108.190748 |url=}}</ref>===
{|class="wikitable"
{| class="wikitable"
|-
|-
| colspan="1" style="text-align:center; background:LightGreen"|[[ACC AHA guidelines classification scheme#Classification of Recommendations|Class I]]
| colspan="1" style="text-align:center; background:LightGreen" |[[ACC AHA guidelines classification scheme#Classification of Recommendations|Class I]]
|-
|-
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''1.''' [[Vasodilator]] therapy is indicated for chronic therapy in patients with severe [[AR]] who have symptoms or [[left ventricular dysfunction]] when surgery is not recommended because of additional cardiac or noncardiac factors. ([[ACC AHA guidelines classification scheme#Level of Evidence|''Level of Evidence: B'']])<nowiki>"</nowiki>
| bgcolor="LightGreen" |<nowiki>"</nowiki>'''1.''' [[Vasodilator]] therapy is indicated for chronic therapy in patients with severe [[AR]] who have symptoms or [[left ventricular dysfunction]] when surgery is not recommended because of additional cardiac or noncardiac factors. ([[ACC AHA guidelines classification scheme#Level of Evidence|''Level of Evidence: B'']])<nowiki>"</nowiki>
|}
|}


{|class="wikitable"
{| class="wikitable"
|-
|-
| colspan="1" style="text-align:center; background:LightCoral"|[[ACC AHA guidelines classification scheme#Classification of Recommendations|Class III]]
| colspan="1" style="text-align:center; background:LightCoral" |[[ACC AHA guidelines classification scheme#Classification of Recommendations|Class III]]
|-
|-
| bgcolor="LightCoral"|
| bgcolor="LightCoral" |
'''1.''' [[Vasodilator]] therapy is not indicated for long-term therapy in asymptomatic patients with mild to moderate [[AR]] and normal [[left ventricular]] systolic function. ([[ACC AHA guidelines classification scheme#Level of Evidence|''Level of Evidence: B'']])<nowiki>"</nowiki>
'''1.''' [[Vasodilator]] therapy is not indicated for long-term therapy in asymptomatic patients with mild to moderate [[AR]] and normal [[left ventricular]] systolic function. ([[ACC AHA guidelines classification scheme#Level of Evidence|''Level of Evidence: B'']])<nowiki>"</nowiki>
|-
|-
| bgcolor="LightCoral"|
| bgcolor="LightCoral" |
'''2.''' [[Vasodilator]] therapy is not indicated for long-term therapy in asymptomatic patients with [[left ventricular]] systolic dysfunction who are otherwise candidates for [[aortic valve replacement]]. ([[ACC AHA guidelines classification scheme#Level of Evidence|''Level of Evidence: C'']])<nowiki>"</nowiki>
'''2.''' [[Vasodilator]] therapy is not indicated for long-term therapy in asymptomatic patients with [[left ventricular]] systolic dysfunction who are otherwise candidates for [[aortic valve replacement]]. ([[ACC AHA guidelines classification scheme#Level of Evidence|''Level of Evidence: C'']])<nowiki>"</nowiki>
|-
|-
| bgcolor="LightCoral"|
| bgcolor="LightCoral" |
'''3.''' [[Vasodilator]] therapy is not indicated for long-term therapy in symptomatic patients with either normal left ventricular function or mild to moderate left ventricular systolic dysfunction who are otherwise candidates for [[aortic valve replacement]]. ([[ACC AHA guidelines classification scheme#Level of Evidence|''Level of Evidence: C'']])<nowiki>"</nowiki>
'''3.''' [[Vasodilator]] therapy is not indicated for long-term therapy in symptomatic patients with either normal left ventricular function or mild to moderate left ventricular systolic dysfunction who are otherwise candidates for [[aortic valve replacement]]. ([[ACC AHA guidelines classification scheme#Level of Evidence|''Level of Evidence: C'']])<nowiki>"</nowiki>
|}
|}


{|class="wikitable"
{| class="wikitable"
|-
|-
| colspan="1" style="text-align:center; background:LemonChiffon"|[[ACC AHA guidelines classification scheme#Classification of Recommendations|Class IIa]]
| colspan="1" style="text-align:center; background:LemonChiffon" |[[ACC AHA guidelines classification scheme#Classification of Recommendations|Class IIa]]
|-
|-
| bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''1.''' [[Vasodilator]] therapy is reasonable for short-term therapy to improve the [[hemodynamic]] profile of patients with severe [[heart failure]] symptoms and severe [[left ventricular dysfunction]] before proceeding with [[aortic valve replacement]]. ([[ACC AHA guidelines classification scheme#Level of Evidence|''Level of Evidence: C'']])<nowiki>"</nowiki>
| bgcolor="LemonChiffon" |<nowiki>"</nowiki>'''1.''' [[Vasodilator]] therapy is reasonable for short-term therapy to improve the [[hemodynamic]] profile of patients with severe [[heart failure]] symptoms and severe [[left ventricular dysfunction]] before proceeding with [[aortic valve replacement]]. ([[ACC AHA guidelines classification scheme#Level of Evidence|''Level of Evidence: C'']])<nowiki>"</nowiki>
|}
|}


{|class="wikitable"
{| class="wikitable"
|-
|-
| colspan="1" style="text-align:center; background:LemonChiffon"|[[ACC AHA guidelines classification scheme#Classification of Recommendations|Class IIb]]
| colspan="1" style="text-align:center; background:LemonChiffon" |[[ACC AHA guidelines classification scheme#Classification of Recommendations|Class IIb]]
|-
|-
| bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''1.''' [[Vasodilator]] therapy may be considered for long-term therapy in asymptomatic patients with severe [[AR]] who have [[left ventricular]] dilatation but normal systolic function. ([[ACC AHA guidelines classification scheme#Level of Evidence|''Level of Evidence: B'']])<nowiki>"</nowiki>
| bgcolor="LemonChiffon" |<nowiki>"</nowiki>'''1.''' [[Vasodilator]] therapy may be considered for long-term therapy in asymptomatic patients with severe [[AR]] who have [[left ventricular]] dilatation but normal systolic function. ([[ACC AHA guidelines classification scheme#Level of Evidence|''Level of Evidence: B'']])<nowiki>"</nowiki>
|}
|}


Latest revision as of 07:59, 19 June 2022
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor-in-Chief: Cafer Zorkun, M.D., Ph.D. [2]; Varun Kumar, M.B.B.S.; Lakshmi Gopalakrishnan, M.B.B.S.; Mohammed A. Sbeih, M.D. [3]; Arooj Naz, M.B.B.S

Overview

In the management of chronic aortic regurgitation, the left ventricular size and function should be monitored closely along with the exercise tolerance of the patient. If the patient develops heart failure symptoms and the disease starts to be symptomatic, then aortic valve replacement or valve repair is indicated. Annual echocardiographic studies are indicated in all patients with significant AR. Vasodilators such as ACE inhibitors, nifedipine, sodium nitroprusside, and hydralazine may slow the rate of progression of AR. The greatest benefit of medical therapy is among symptomatic patients and those with heart failure symptoms due to advanced disease, but in general, medical therapy has a limited role in AR because symptomatic cases should be treated with valve replacement if the patient is a good candidate for surgery. Warfarin and long-term anticoagulation is not recommended in AR if there are no other indications for anticoagulation.[1]

Medical Therapy

Medical therapy of chronic AR involves the use of vasodilators. Small trials have demonstrated a benefit from the administration of ACE inhibitors, nifedipine, sodium nitroprusside, and hydralazine in improving left ventricular wall stress, ejection fraction, and left ventricular mass.[2][3][4][5] The use of these vasodilators is indicated only in those individuals who suffer from hypertension in addition to AR. The goal in using these pharmacologic agents is to decrease the afterload so that the left ventricle is unloaded. This results in reduction in left ventricular end diastolic pressure thereby preserving the left ventricular systolic function and also benefits the patients in left ventricular failure secondary to AR.

Long term therapy with nifedipine and hydralazine have shown to increase left ventricular ejection fraction, reduce left ventricular end diastolic volume, and reduction in left ventricular mass thereby delaying the need for valve surgery.[6][7][8] While ACE inhibitors such as enalapril and quinapril have shown to decrease left ventricular mass and end diastolic volume but with no influence on ejection fraction.[9][10]

Patients with severe AR with normal left ventricular function are recommended to undergo surgery though there are no sufficient evidences against medical management.

Use of drugs other than vasodilators, such as digoxin, diuretics, and other positive inotropic drugs for long term treatment have no supporting data. Beta blockers are relatively contraindicated since they decrease heart rate and prolong diastolic phase. There by increasing the back flow of blood from aorta. However, beta blockers can be considered in patients with bicuspid aortic valve with mild AR and aortic root diameter of more than 40mm.[11]

2020 AHA/ACC Guideline for the Management of Patients With Valvular Heart Diseases [12]

Class I
"1. Treatment of hypertension (systolic BP >140 mm Hg) is recommended in patients with chronic AR (stages B and C), preferably with dihydropyridine calcium channel blockers or ACE inhibitors/angiotensin-receptor blockers (ARBs) (Level of Evidence:B). Severe AR with symptoms and or LV systolic dysfunction (Stages C2 and D)that have surgical risk, LVEF is reduced with ACE inhibitors, ARBs, and/or sacubitril/valsartan'[13]
Class IIa
"1. Medical therapy with ACE inhibitors/ARBs and beta blockers is reasonable in patients with severe AR who have symptoms and/or LV dysfunction (stages C2 and D) when surgery is not performed because of comorbidities (Level of Evidence: B) "

2008 Focused Update Incorporated into the 2006 ACC/AHA Guidelines for the Management of Patients with Valvular Heart Disease (DO NOT EDIT)[11]

Vasodilator Therapy (DO NOT EDIT)[11]

Class I
"1. Vasodilator therapy is indicated for chronic therapy in patients with severe AR who have symptoms or left ventricular dysfunction when surgery is not recommended because of additional cardiac or noncardiac factors. (Level of Evidence: B)"
Class III

1. Vasodilator therapy is not indicated for long-term therapy in asymptomatic patients with mild to moderate AR and normal left ventricular systolic function. (Level of Evidence: B)"

2. Vasodilator therapy is not indicated for long-term therapy in asymptomatic patients with left ventricular systolic dysfunction who are otherwise candidates for aortic valve replacement. (Level of Evidence: C)"

3. Vasodilator therapy is not indicated for long-term therapy in symptomatic patients with either normal left ventricular function or mild to moderate left ventricular systolic dysfunction who are otherwise candidates for aortic valve replacement. (Level of Evidence: C)"

Class IIa
"1. Vasodilator therapy is reasonable for short-term therapy to improve the hemodynamic profile of patients with severe heart failure symptoms and severe left ventricular dysfunction before proceeding with aortic valve replacement. (Level of Evidence: C)"
Class IIb
"1. Vasodilator therapy may be considered for long-term therapy in asymptomatic patients with severe AR who have left ventricular dilatation but normal systolic function. (Level of Evidence: B)"

References

  1. ↑ Salem DN, O'Gara PT, Madias C, et al. Valvular and structural heart disease: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 2008; 133:593S
  2. ↑ Bolen JL, Alderman EL (1976). "Hemodynamic consequences of afterload reduction in patients with chronic aortic regurgitation". Circulation. 53 (5): 879–83. PMID 1260993. Retrieved 2011-03-23. Unknown parameter |month= ignored (help)
  3. ↑ Miller RR, Vismara LA, DeMaria AN, Salel AF, Mason DT (1976). "Afterload reduction therapy with nitroprusside in severe aortic regurgitation: improved cardiac performance and reduced regurgitant volume". The American Journal of Cardiology. 38 (5): 564–7. PMID 983953. Unknown parameter |month= ignored (help); |access-date= requires |url= (help)
  4. ↑ Greenberg BH, DeMots H, Murphy E, Rahimtoola S (1980). "Beneficial effects of hydralazine on rest and exercise hemodynamics in patients with chronic severe AR". Circulation. 62 (1): 49–55. PMID 7379285. Retrieved 2011-03-23. Unknown parameter |month= ignored (help)
  5. ↑ Fioretti P, Benussi B, Scardi S, Klugmann S, Brower RW, Camerini F (1982). "Afterload reduction with nifedipine in AR". The American Journal of Cardiology. 49 (7): 1728–32. PMID 7081058. Unknown parameter |month= ignored (help); |access-date= requires |url= (help)
  6. ↑ Scognamiglio R, Rahimtoola SH, Fasoli G, Nistri S, Dalla Volta S (1994). "Nifedipine in asymptomatic patients with severe aortic regurgitation and normal left ventricular function". The New England Journal of Medicine. 331 (11): 689–94. doi:10.1056/NEJM199409153311101. PMID 8058074. Retrieved 2011-03-23. Unknown parameter |month= ignored (help)
  7. ↑ Greenberg B, Massie B, Bristow JD, Cheitlin M, Siemienczuk D, Topic N, Wilson RA, Szlachcic J, Thomas D (1988). "Long-term vasodilator therapy of chronic AR. A randomized double-blinded, placebo-controlled clinical trial". Circulation. 78 (1): 92–103. PMID 3289791. Retrieved 2011-03-23. Unknown parameter |month= ignored (help)
  8. ↑ Scognamiglio R, Fasoli G, Ponchia A, Dalla-Volta S (1990). "Long-term nifedipine unloading therapy in asymptomatic patients with chronic severe aortic regurgitation". Journal of the American College of Cardiology. 16 (2): 424–9. PMID 2197314. Retrieved 2011-03-23. Unknown parameter |month= ignored (help)
  9. ↑ Lin M, Chiang HT, Lin SL, Chang MS, Chiang BN, Kuo HW, Cheitlin MD (1994). "Vasodilator therapy in chronic asymptomatic aortic regurgitation: enalapril versus hydralazine therapy". Journal of the American College of Cardiology. 24 (4): 1046–53. PMID 7930196. Retrieved 2011-03-23. Unknown parameter |month= ignored (help)
  10. ↑ Schön HR, Dorn R, Barthel P, Schömig A (1994). "Effects of 12 months quinapril therapy in asymptomatic patients with chronic aortic regurgitation". The Journal of Heart Valve Disease. 3 (5): 500–9. PMID 8000584. Unknown parameter |month= ignored (help); |access-date= requires |url= (help)
  11. ↑ 11.0 11.1 11.2 Bonow RO, Carabello BA, Chatterjee K, de Leon AC, Faxon DP, Freed MD, Gaasch WH, Lytle BW, Nishimura RA, O'Gara PT, O'Rourke RA, Otto CM, Shah PM, Shanewise JS (2008). "2008 Focused update incorporated into the ACC/AHA 2006 guidelines 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 (Writing Committee to Revise the 1998 Guidelines for the Management of Patients With Valvular Heart Disease): endorsed by the Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons". Circulation. 118 (15): e523–661. doi:10.1161/CIRCULATIONAHA.108.190748. PMID 18820172. Retrieved 2011-03-24. Unknown parameter |month= ignored (help)
  12. ↑ "2014 AHA/ACC Guideline for the Management of Patients With Valvular Heart Disease: Executive Summary". Retrieved 4 March 2014.
  13. ↑ https://www.ahajournals.org/doi/10.1161/CIR.0000000000000923#d1e5782. Missing or empty |title= (help)

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