Aortic insufficiency medical management: Difference between revisions
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'''Associate Editor-In-Chief:''' {{CZ}}; [[Varun Kumar]], M.B.B.S.; [[Lakshmi Gopalakrishnan]], M.B.B.S. | '''Associate Editor-In-Chief:''' {{CZ}}; [[Varun Kumar]], M.B.B.S.; [[Lakshmi Gopalakrishnan]], M.B.B.S. | ||
Medical therapy of chronic aortic insufficiency involves the use of [[vasodilators]]. Small trials have demonstrated a benefit from the administration of [[ACE inhibitor]]s, [[nifedipine]], [[sodium nitroprusside]] and [[hydralazine]] in improving left ventricular wall stress, [[ejection fraction]], and left ventricular mass <ref name="pmid1260993">{{cite journal |author=Bolen JL, Alderman EL |title=Hemodynamic consequences of afterload reduction in patients with chronic aortic regurgitation |journal=[[Circulation]] |volume=53 |issue=5 |pages=879–83 |year=1976 |month=May |pmid=1260993 |doi= |url=http://circ.ahajournals.org/cgi/pmidlookup?view=long&pmid=1260993 |accessdate=2011-03-23}}</ref> <ref name="pmid983953">{{cite journal |author=Miller RR, Vismara LA, DeMaria AN, Salel AF, Mason DT |title=Afterload reduction therapy with nitroprusside in severe aortic regurgitation: improved cardiac performance and reduced regurgitant volume |journal=[[The American Journal of Cardiology]] |volume=38 |issue=5 |pages=564–7 |year=1976 |month=November |pmid=983953 |doi= |url= |accessdate=2011-03-23}}</ref> <ref name="pmid7379285">{{cite journal |author=Greenberg BH, DeMots H, Murphy E, Rahimtoola S |title=Beneficial effects of hydralazine on rest and exercise hemodynamics in patients with chronic severe aortic insufficiency |journal=[[Circulation]] |volume=62 |issue=1 |pages=49–55 |year=1980 |month=July |pmid=7379285 |doi= |url=http://circ.ahajournals.org/cgi/pmidlookup?view=long&pmid=7379285 |accessdate=2011-03-23}}</ref> <ref name="pmid7081058">{{cite journal |author=Fioretti P, Benussi B, Scardi S, Klugmann S, Brower RW, Camerini F |title=Afterload reduction with nifedipine in aortic insufficiency |journal=[[The American Journal of Cardiology]] |volume=49 |issue=7 |pages=1728–32 |year=1982 |month=May |pmid=7081058 |doi= |url= |accessdate=2011-03-23}}</ref>. The use of these vasodilators is indicated only in those individuals who suffer from [[hypertension]] in addition to aortic insufficiency. 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 aortic insufficiency. | Medical therapy of chronic aortic insufficiency involves the use of [[vasodilators]]. Small trials have demonstrated a benefit from the administration of [[ACE inhibitor]]s, [[nifedipine]], [[sodium nitroprusside]] and [[hydralazine]] in improving left ventricular wall stress, [[ejection fraction]], and left ventricular mass <ref name="pmid1260993">{{cite journal |author=Bolen JL, Alderman EL |title=Hemodynamic consequences of afterload reduction in patients with chronic aortic regurgitation |journal=[[Circulation]] |volume=53 |issue=5 |pages=879–83 |year=1976 |month=May |pmid=1260993 |doi= |url=http://circ.ahajournals.org/cgi/pmidlookup?view=long&pmid=1260993 |accessdate=2011-03-23}}</ref> <ref name="pmid983953">{{cite journal |author=Miller RR, Vismara LA, DeMaria AN, Salel AF, Mason DT |title=Afterload reduction therapy with nitroprusside in severe aortic regurgitation: improved cardiac performance and reduced regurgitant volume |journal=[[The American Journal of Cardiology]] |volume=38 |issue=5 |pages=564–7 |year=1976 |month=November |pmid=983953 |doi= |url= |accessdate=2011-03-23}}</ref> <ref name="pmid7379285">{{cite journal |author=Greenberg BH, DeMots H, Murphy E, Rahimtoola S |title=Beneficial effects of hydralazine on rest and exercise hemodynamics in patients with chronic severe aortic insufficiency |journal=[[Circulation]] |volume=62 |issue=1 |pages=49–55 |year=1980 |month=July |pmid=7379285 |doi= |url=http://circ.ahajournals.org/cgi/pmidlookup?view=long&pmid=7379285 |accessdate=2011-03-23}}</ref> <ref name="pmid7081058">{{cite journal |author=Fioretti P, Benussi B, Scardi S, Klugmann S, Brower RW, Camerini F |title=Afterload reduction with nifedipine in aortic insufficiency |journal=[[The American Journal of Cardiology]] |volume=49 |issue=7 |pages=1728–32 |year=1982 |month=May |pmid=7081058 |doi= |url= |accessdate=2011-03-23}}</ref>. The use of these vasodilators is indicated only in those individuals who suffer from [[hypertension]] in addition to aortic insufficiency. 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 aortic insufficiency. | ||
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'''Risk Stratification'''<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=2011-03-25}}</ref> | '''Risk Stratification'''<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=2011-03-25}}</ref> | ||
'''High risk:''' Aortic insufficiency associated with NYHA class III to IV symptoms, [[Marfan syndrome]] or left ventricular [[ejection fraction]] of less than 40%. Such patients ideally should undergo definitive surgical therapy before pregnancy. | '''High risk:''' Aortic insufficiency associated with [[NYHA class]] III to IV symptoms, [[Marfan syndrome]] or left ventricular [[ejection fraction]] of less than 40%. Such patients ideally should undergo definitive surgical therapy before pregnancy. If patient is already pregnant, termination of pregnancy is recommended. | ||
'''Low risk:''' Aortic insufficiency associated with NYHA class I to II symptoms. Such women generally tolerate pregnancy without complications and the natural fall in [[systolic blood pressure]] during pregnancy may be beneficial in reducing the regurgitant volume. | '''Low risk:''' Aortic insufficiency associated with [[NYHA class]] I to II symptoms. Such women generally tolerate pregnancy without complications and the natural fall in [[systolic blood pressure]] during pregnancy may be beneficial in reducing the regurgitant volume. | ||
Aortic root dilatation in pregnant patients with [[Marfan syndrome]] are at increased risk of developing [[aortic dissection]] or rupture. Patients are at high risk if '''aortic root diameter is greater than 40mm''' with approximately 10% probability of developing aortic dissection<ref name="pmid12800857">{{cite journal |author= |title=Expert consensus document on management of cardiovascular diseases during pregnancy |journal=[[European Heart Journal]] |volume=24 |issue=8 |pages=761–81 |year=2003 |month=April |pmid=12800857 |doi= |url=http://eurheartj.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=12800857 |accessdate=2011-03-25}}</ref> <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=2011-03-25}}</ref>. Women with marfan syndrome should be counseled against pregnancy. However, replacement of aortic root and ascending aorta may be considered if the aortic diameter exceeds 40 mm in women with [[marfan syndrome]] who are contemplating pregnancy<ref name="pmid20233780">{{cite journal |author=Hiratzka LF, Bakris GL, Beckman JA, Bersin RM, Carr VF, Casey DE, Eagle KA, Hermann LK, Isselbacher EM, Kazerooni EA, Kouchoukos NT, Lytle BW, Milewicz DM, Reich DL, Sen S, Shinn JA, Svensson LG, Williams DM |title=2010 ACCF/AHA/AATS/ACR/ASA/SCA/SCAI/SIR/STS/SVM guidelines for the diagnosis and management of patients with Thoracic Aortic Disease: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines, American Association for Thoracic Surgery, American College of Radiology, American Stroke Association, Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, Society of Interventional Radiology, Society of Thoracic Surgeons, and Society for Vascular Medicine |journal=[[Circulation]] |volume=121 |issue=13 |pages=e266–369 |year=2010 |month=April |pmid=20233780 |doi=10.1161/CIR.0b013e3181d4739e |url=http://circ.ahajournals.org/cgi/pmidlookup?view=long&pmid=20233780 |accessdate=2011-03-25}}</ref>. | Aortic root dilatation in pregnant patients with [[Marfan syndrome]] are at increased risk of developing [[aortic dissection]] or rupture which usually occur in third trimister or near time of delivery. Patients are at high risk if '''aortic root diameter is greater than 40mm''' with approximately 10% probability of developing aortic dissection<ref name="pmid12800857">{{cite journal |author= |title=Expert consensus document on management of cardiovascular diseases during pregnancy |journal=[[European Heart Journal]] |volume=24 |issue=8 |pages=761–81 |year=2003 |month=April |pmid=12800857 |doi= |url=http://eurheartj.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=12800857 |accessdate=2011-03-25}}</ref> <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=2011-03-25}}</ref>. Women with marfan syndrome should be counseled against pregnancy and should undergo screening [[transthoracic echocardiogram]] to assess the aortic root dimensions. However, replacement of aortic root and ascending aorta may be considered if the aortic diameter exceeds 40 mm in women with [[marfan syndrome]] who are contemplating pregnancy<ref name="pmid20233780">{{cite journal |author=Hiratzka LF, Bakris GL, Beckman JA, Bersin RM, Carr VF, Casey DE, Eagle KA, Hermann LK, Isselbacher EM, Kazerooni EA, Kouchoukos NT, Lytle BW, Milewicz DM, Reich DL, Sen S, Shinn JA, Svensson LG, Williams DM |title=2010 ACCF/AHA/AATS/ACR/ASA/SCA/SCAI/SIR/STS/SVM guidelines for the diagnosis and management of patients with Thoracic Aortic Disease: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines, American Association for Thoracic Surgery, American College of Radiology, American Stroke Association, Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, Society of Interventional Radiology, Society of Thoracic Surgeons, and Society for Vascular Medicine |journal=[[Circulation]] |volume=121 |issue=13 |pages=e266–369 |year=2010 |month=April |pmid=20233780 |doi=10.1161/CIR.0b013e3181d4739e |url=http://circ.ahajournals.org/cgi/pmidlookup?view=long&pmid=20233780 |accessdate=2011-03-25}}</ref>. [[Beta blockers]] can be used prophylactically throughout pregnancy with [[labetalol]] or [[metoprolol]] being the preferred drugs <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=2011-03-27}}</ref>. As per AHA/ACC 2006 guidelines, serial transthoracic [[echocardiogram]] and regular monitoring of [[blood pressure]] throughout the pregnancy with providing adequate [[analgesia]] during labor are recommended. Shortening of [[second stage of labor]] using various obstetric techniques may be beneficial. | ||
In patients with an aortic root diameter greater than 40 mm, severe [[aortic regurgitation]], [[heart failure]] or [[aortic dissection]], [[cesarean delivery]] with [[general anesthesia]] is preferred as it allows optimal hemodynamic control.<ref name="pmid20233780">{{cite journal |author=Hiratzka LF, Bakris GL, Beckman JA, Bersin RM, Carr VF, Casey DE, Eagle KA, Hermann LK, Isselbacher EM, Kazerooni EA, Kouchoukos NT, Lytle BW, Milewicz DM, Reich DL, Sen S, Shinn JA, Svensson LG, Williams DM |title=2010 ACCF/AHA/AATS/ACR/ASA/SCA/SCAI/SIR/STS/SVM guidelines for the diagnosis and management of patients with Thoracic Aortic Disease: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines, American Association for Thoracic Surgery, American College of Radiology, American Stroke Association, Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, Society of Interventional Radiology, Society of Thoracic Surgeons, and Society for Vascular Medicine |journal=[[Circulation]] |volume=121 |issue=13 |pages=e266–369 |year=2010 |month=April |pmid=20233780 |doi=10.1161/CIR.0b013e3181d4739e |url=http://circ.ahajournals.org/cgi/pmidlookup?view=long&pmid=20233780 |accessdate=2011-03-27}}</ref> <ref name="pmid7778824">{{cite journal |author=Elkayam U, Ostrzega E, Shotan A, Mehra A |title=Cardiovascular problems in pregnant women with the Marfan syndrome |journal=[[Annals of Internal Medicine]] |volume=123 |issue=2 |pages=117–22 |year=1995 |month=July |pmid=7778824 |doi= |url=http://www.annals.org/cgi/pmidlookup?view=long&pmid=7778824 |accessdate=2011-03-27}}</ref> | |||
==References== | ==References== | ||
{{reflist|2}} | {{reflist|2}} | ||
{{WH}} | {{WH}} | ||
{{WS}} | {{WS}} | ||
[[CME Category::Cardiology]] | |||
[[Category:Cardiology]] | |||
Latest revision as of 22:45, 14 March 2016
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.
Medical therapy of chronic aortic insufficiency 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 [1] [2] [3] [4]. The use of these vasodilators is indicated only in those individuals who suffer from hypertension in addition to aortic insufficiency. 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 aortic insufficiency.
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 [5] [6] [7]. 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 [8] [9]
Patients with severe aortic insufficiency 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 aortic insufficiency and aortic root diameter of more than 40mm [10].
ACC/AHA guidelines for use of Vasodilator therapy in Chronic severe Aortic Insufficiency
| “ | Class I
Vasodilator therapy is indicated for chronic therapy in patients with severe aortic insufficiency who have symptoms or left ventricular dysfunction when surgery is not recommended because of additional cardiac or noncardiac factors. Class IIa 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. Class IIb Vasodilator therapy may be considered for long-term therapy in asymptomatic patients with severe aortic insufficiency who have left ventricular dilatation but normal systolic function. Class III
|
” |
Prophylactic antibiotics prior dental procedures are not recommended for all patients with aortic insufficiency as per 2007 AHA guidelines (for infective endocarditis) unless there are other indications.
Aortic insufficiency in pregnancy
Isolated aortic insufficiency in pregnant patients can be managed with combination of diuretics and vasodilators[11]. ACE inhibitors are contraindicated in pregnancy. Patients with signs and symptoms of left ventricular failure should be monitored throughout labor and delivery with strict attention to volume status and blood pressure.
Risk Stratification[10]
High risk: Aortic insufficiency associated with NYHA class III to IV symptoms, Marfan syndrome or left ventricular ejection fraction of less than 40%. Such patients ideally should undergo definitive surgical therapy before pregnancy. If patient is already pregnant, termination of pregnancy is recommended.
Low risk: Aortic insufficiency associated with NYHA class I to II symptoms. Such women generally tolerate pregnancy without complications and the natural fall in systolic blood pressure during pregnancy may be beneficial in reducing the regurgitant volume.
Aortic root dilatation in pregnant patients with Marfan syndrome are at increased risk of developing aortic dissection or rupture which usually occur in third trimister or near time of delivery. Patients are at high risk if aortic root diameter is greater than 40mm with approximately 10% probability of developing aortic dissection[12] [10]. Women with marfan syndrome should be counseled against pregnancy and should undergo screening transthoracic echocardiogram to assess the aortic root dimensions. However, replacement of aortic root and ascending aorta may be considered if the aortic diameter exceeds 40 mm in women with marfan syndrome who are contemplating pregnancy[13]. Beta blockers can be used prophylactically throughout pregnancy with labetalol or metoprolol being the preferred drugs [10]. As per AHA/ACC 2006 guidelines, serial transthoracic echocardiogram and regular monitoring of blood pressure throughout the pregnancy with providing adequate analgesia during labor are recommended. Shortening of second stage of labor using various obstetric techniques may be beneficial. In patients with an aortic root diameter greater than 40 mm, severe aortic regurgitation, heart failure or aortic dissection, cesarean delivery with general anesthesia is preferred as it allows optimal hemodynamic control.[13] [14]
References
- ↑ 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) - ↑ 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) - ↑ Greenberg BH, DeMots H, Murphy E, Rahimtoola S (1980). "Beneficial effects of hydralazine on rest and exercise hemodynamics in patients with chronic severe aortic insufficiency". Circulation. 62 (1): 49–55. PMID 7379285. Retrieved 2011-03-23. Unknown parameter
|month=ignored (help) - ↑ Fioretti P, Benussi B, Scardi S, Klugmann S, Brower RW, Camerini F (1982). "Afterload reduction with nifedipine in aortic insufficiency". The American Journal of Cardiology. 49 (7): 1728–32. PMID 7081058. Unknown parameter
|month=ignored (help);|access-date=requires|url=(help) - ↑ 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) - ↑ 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 aortic insufficiency. A randomized double-blinded, placebo-controlled clinical trial". Circulation. 78 (1): 92–103. PMID 3289791. Retrieved 2011-03-23. Unknown parameter
|month=ignored (help) - ↑ 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) - ↑ 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) - ↑ 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) - ↑ 10.0 10.1 10.2 10.3 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) - ↑ Sheikh F, Rangwala S, DeSimone C, Smith HS, O'Leary AM (1995). "Management of the parturient with severe aortic incompetence". Journal of Cardiothoracic and Vascular Anesthesia. 9 (5): 575–7. PMID 8547563. Retrieved 2011-03-25. Unknown parameter
|month=ignored (help) - ↑ "Expert consensus document on management of cardiovascular diseases during pregnancy". European Heart Journal. 24 (8): 761–81. 2003. PMID 12800857. Retrieved 2011-03-25. Unknown parameter
|month=ignored (help) - ↑ 13.0 13.1 Hiratzka LF, Bakris GL, Beckman JA, Bersin RM, Carr VF, Casey DE, Eagle KA, Hermann LK, Isselbacher EM, Kazerooni EA, Kouchoukos NT, Lytle BW, Milewicz DM, Reich DL, Sen S, Shinn JA, Svensson LG, Williams DM (2010). "2010 ACCF/AHA/AATS/ACR/ASA/SCA/SCAI/SIR/STS/SVM guidelines for the diagnosis and management of patients with Thoracic Aortic Disease: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines, American Association for Thoracic Surgery, American College of Radiology, American Stroke Association, Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, Society of Interventional Radiology, Society of Thoracic Surgeons, and Society for Vascular Medicine". Circulation. 121 (13): e266–369. doi:10.1161/CIR.0b013e3181d4739e. PMID 20233780. Retrieved 2011-03-25. Unknown parameter
|month=ignored (help) - ↑ Elkayam U, Ostrzega E, Shotan A, Mehra A (1995). "Cardiovascular problems in pregnant women with the Marfan syndrome". Annals of Internal Medicine. 123 (2): 117–22. PMID 7778824. Retrieved 2011-03-27. Unknown parameter
|month=ignored (help)