Aortic stenosis cardiac catheterization: Difference between revisions
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*The femoral pressure is usually measured off of the sidearm of the femoral sheath. The sheath size of the femoral sheath should be at least on French size larger than the catheter so that the catheter does not induce dampening of the pressure waveform in the femoral sheath. | *The femoral pressure is usually measured off of the sidearm of the femoral sheath. The sheath size of the femoral sheath should be at least on French size larger than the catheter so that the catheter does not induce dampening of the pressure waveform in the femoral sheath. | ||
*It is assumed that the femoral blood pressure is equal to the blood pressure in the aorta just distal to the aortic valve. This assumption is often wrong. Prior to crossing the aortic valve, the blood pressure should be compared in the proximal aorta and the femoral sheath. As a result of the reflection of the waveforms in stiff atherosclerotic blood vessel, there may be a higher pressure in the femoral sheath. This is termed femoral augmentation. The augmentation of the femoral blood pressure must be subtracted from the peak gradient in calculating the [[aortic valve area]]. On the other hand, the pressure in the femoral artery may be lower than that of the central aorta due to peripheral arterial disease. In this scenario, the femoral pressure must be upwardly adjusted to account for this. | *It is assumed that the femoral blood pressure is equal to the blood pressure in the aorta just distal to the aortic valve. This assumption is often wrong. Prior to crossing the aortic valve, the blood pressure should be compared in the proximal aorta and the femoral sheath. As a result of the reflection of the waveforms in stiff atherosclerotic blood vessel, there may be a higher pressure in the femoral sheath. This is termed femoral augmentation. The augmentation of the femoral blood pressure must be subtracted from the peak gradient in calculating the [[aortic valve area]]. On the other hand, the pressure in the femoral artery may be lower than that of the central aorta due to peripheral arterial disease. In this scenario, the femoral pressure must be upwardly adjusted to account for this. | ||
*Fluid dynamic mediated subvalvular pressure gradients are often present in patients with [[severe aortic stenosis]] in the absence of an anatomic [[Subvalvular aortic stenosis|subvalvular obstruction]] and constitute ~50% of the total measured transvalvular gradient. The extent of increase in [[cardiac output]] during exercise is inversely related to the magnitude of subvalvular gradient.<ref name="pmid11524395">{{cite journal |author=Laskey WK, Kussmaul WG |title=Subvalvular gradients in patients with valvular aortic stenosis: prevalence, magnitude, and physiological importance |journal=[[Circulation]] |volume=104 |issue=9 |pages=1019–22 |year=2001 |month=August |pmid=11524395 |doi= |url=http://circ.ahajournals.org/cgi/pmidlookup?view=long&pmid=11524395 |accessdate=2012-04-12}}</ref> | |||
===Assessment of the Aortic Valve Area=== | |||
*Simultaneous measurement of [[Cardiac output|left ventricular output]] ''(measures the flow through the aortic valve)'' and the [[Intravascular pressure gradient|pressure gradient]] across the aortic valve provides the variables that are required to calculate the aortic valve area.<ref>Hirshfeld JW, Kolansky DM. Valve function: Stenosis and regurgitation. In: Diagnostic and Therapeutic Cardiac Catheterization, 2nd ed, Pepine CJ, Hill JA, Lambert CR (Eds), Williams & Wilkins, Baltimore 1994. p.443</ref><ref>Carabello BA, Grossman W. Calculation of stenotic valve orifice area. In: Cardiac Catheterization and Angiography, 3rd ed, Grossman W (Ed), Lea and Febiger, Philadelphia 1986. p.143.</ref> | |||
*According to the current recommendations, following [[dobutamine|dobutamine infusion]], if the aortic valve area increases to >1.2 cm<sup>2</sup>, and the mean pressure gradient rises above 30 mmHg, such patients may benefit from [[aortic valve replacement]]. Failure to achieve these improvements has shown to be associated with higher early surgical mortality in comparison to patients who can augment their contractility and gradient: '''32-33% versus 5-7%''', respectively. Additionally, 5-year survival was lower in patients who could not augment their contractility in comparison to those who could: '''10–25% versus 88%''', respectively. | |||
*Aortic valve area can be calculated by the following two equations: | |||
=====[[Aortic valve area calculation#Gorlin Equation|Gorlin Equation:]]===== | |||
<blockquote>[[Aortic valve area|Aortic Valve Area (cms<sup>2</sup>)]] '''=''' '''('''[[Stroke volume|Stroke volume (mL/beat)]] '''÷''' [[ejection fraction|Systolic ejection period (secs/beat)]]''')''' '''÷''' '''(''' 44.3 '''x''' square root of [[Intravascular pressure gradient|mean systolic pressure gradient]] between the [[left ventricle]] and [[aorta]] [[mmHg|(mmHg)]]''')'''</blockquote> | |||
=====[[Aortic valve area calculation#Hakki Equation|Hakki Equation:]]===== | |||
<blockquote> [[Aortic valve area|Aortic Valve Area (cms<sup>2</sup>)]] '''=''' '''('''[[Cardiac output|Cardiac output (liters/minute)]]''')''' '''÷''' '''('''Square root of [[Intravascular pressure gradient|mean systolic pressure gradient]] between the [[left ventricle]] and [[aorta]] [[mmHg|(mmHg)]]''')'''</blockquote> | |||
===Assessment of the Aortic Valve Resistance:=== | |||
**Simultaneous measurement of [[Cardiac output|left ventricular output]] ''(measures the flow through the aortic valve)'' and the [[Intravascular pressure gradient|pressure gradient]] across the aortic valve provides the variables that are required to calculate the aortic valve resistance.<ref>Hirshfeld JW, Kolansky DM. Valve function: Stenosis and regurgitation. In: Diagnostic and Therapeutic Cardiac Catheterization, 2nd ed, Pepine CJ, Hill JA, Lambert CR (Eds), Williams & Wilkins, Baltimore 1994. p.443</ref><ref>Carabello BA, Grossman W. Calculation of stenotic valve orifice area. In: Cardiac Catheterization and Angiography, 3rd ed, Grossman W (Ed), Lea and Febiger, Philadelphia 1986. p.143.</ref> | |||
*Cannon JD Jr et al, described the benefit of calculating aortic valve resistance in conjunction with the [[Aortic valve area calculation#Gorlin Equation|Gorlin formula]] to differentiate patients with true [[severe aortic stenosis]] from those with [[mild aortic stenosis]].<ref name="pmid1452925">{{cite journal |author=Cannon JD, Zile MR, Crawford FA, Carabello BA |title=Aortic valve resistance as an adjunct to the Gorlin formula in assessing the severity of aortic stenosis in symptomatic patients |journal=[[Journal of the American College of Cardiology]] |volume=20 |issue=7 |pages=1517–23 |year=1992 |month=December |pmid=1452925 |doi= |url=http://linkinghub.elsevier.com/retrieve/pii/0735-1097(92)90445-S |accessdate=2012-04-12}}</ref> The clinical implication of this differentiation is that patients with [[mild aortic stenosis]] may not benefit from [[aortic valve replacement]]. | |||
*Patients with high [[cardiac output]] with minimal or no increase in [[Intravascular pressure gradient|pressure gradient]] also fall into the category of [[mild aortic stenosis]] and may not benefit from [[aortic valve replacement]]. | |||
*Furthermore, aortic valve resistance is less flow-dependent than aortic valve area which is of particular benefit in patients with [[Aortic stenosis pathophysiology#Low Flow, Low Gradient, Low Ejection Fraction Aortic Stenosis|low output aortic stenosis]].<ref name="pmid1452925">{{cite journal |author=Cannon JD, Zile MR, Crawford FA, Carabello BA |title=Aortic valve resistance as an adjunct to the Gorlin formula in assessing the severity of aortic stenosis in symptomatic patients |journal=[[Journal of the American College of Cardiology]] |volume=20 |issue=7 |pages=1517–23 |year=1992 |month=December |pmid=1452925 |doi= |url=http://linkinghub.elsevier.com/retrieve/pii/0735-1097(92)90445-S |accessdate=2012-04-12}}</ref> | |||
*Aortic valve resistance can be calculated using the equation:<ref name="pmid8916482">{{cite journal |author=Badano L, Cassottano P, Bertoli D, Carratino L, Lucatti A, Spirito P |title=Changes in effective aortic valve area during ejection in adults with aortic stenosis |journal=[[The American Journal of Cardiology]] |volume=78 |issue=9 |pages=1023–8 |year=1996 |month=November |pmid=8916482 |doi= |url=http://linkinghub.elsevier.com/retrieve/pii/S0002914996005280 |accessdate=2012-04-12}}</ref><ref name="pmid2295132">{{cite journal |author=Ford LE, Feldman T, Chiu YC, Carroll JD |title=Hemodynamic resistance as a measure of functional impairment in aortic valvular stenosis |journal=[[Circulation Research]] |volume=66 |issue=1 |pages=1–7 |year=1990 |month=January |pmid=2295132 |doi= |url=http://circres.ahajournals.org/cgi/pmidlookup?view=long&pmid=2295132 |accessdate=2012-04-12}}</ref> | |||
<blockquote>'''Aortic Valve Resistance (dyne seconds per cms<sup>5</sup>)''' '''=''' '''{''' '''('''[[Intravascular pressure gradient|Mean Pressure Gradient]] between the [[left ventricle]] and [[aorta]] [[mmHg|(mmHg)]] '''x''' [[heart rate|Heart Rate (beats/min)]] '''x''' [[ejection fraction|Systolic ejection period (secs/beat)]] ''')''' '''÷''' [[Cardiac output]] '''}''' '''x''' '''1.33'''</blockquote> | |||
*Unsteady fluid-dynamics support the use of [[aortic valve area calculation]] over other measures of aortic stenosis including aortic valve resistance.<ref name="pmid12150306">{{cite journal |author=Bermejo J, Antoranz JC, Burwash IG, Alvarez JL, Moreno M, García-Fernández MA, Otto CM |title=In-vivo analysis of the instantaneous transvalvular pressure difference-flow relationship in aortic valve stenosis: implications of unsteady fluid-dynamics for the clinical assessment of disease severity |journal=[[The Journal of Heart Valve Disease]] |volume=11 |issue=4 |pages=557–66 |year=2002 |month=July |pmid=12150306 |doi= |url= |accessdate=2012-04-12}}</ref><ref name="pmid16386676">{{cite journal |author=Kadem L, Rieu R, Dumesnil JG, Durand LG, Pibarot P |title=Flow-dependent changes in Doppler-derived aortic valve effective orifice area are real and not due to artifact |journal=[[Journal of the American College of Cardiology]] |volume=47 |issue=1 |pages=131–7 |year=2006 |month=January |pmid=16386676 |doi=10.1016/j.jacc.2005.05.100 |url=http://linkinghub.elsevier.com/retrieve/pii/S0735-1097(05)02358-2 |accessdate=2012-04-12}}</ref><ref name="pmid16750677">{{cite journal |author=Otto CM |title=Valvular aortic stenosis: disease severity and timing of intervention |journal=[[Journal of the American College of Cardiology]] |volume=47 |issue=11 |pages=2141–51 |year=2006 |month=June |pmid=16750677 |doi=10.1016/j.jacc.2006.03.002 |url=http://linkinghub.elsevier.com/retrieve/pii/S0735-1097(06)00617-6 |accessdate=2012-04-12}}</ref> | |||
===Crossing the Stenosed Aortic Valve=== | ===Crossing the Stenosed Aortic Valve=== |
Revision as of 17:25, 21 November 2012
Aortic Stenosis Microchapters |
Diagnosis |
---|
Treatment |
Percutaneous Aortic Balloon Valvotomy (PABV) or Aortic Valvuloplasty |
Transcatheter Aortic Valve Replacement (TAVR) |
Case Studies |
Aortic stenosis cardiac catheterization On the Web |
American Roentgen Ray Society Images of Aortic stenosis cardiac catheterization |
Directions to Hospitals Treating Aortic stenosis cardiac catheterization |
Risk calculators and risk factors for Aortic stenosis cardiac catheterization |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-In-Chief: Mohammed A. Sbeih, M.D. [2]; Assistant Editor-In-Chief: Kristin Feeney, B.S. [3]
Overview
Left and right heart catheterization as well as angiography may be useful in the assessment of the patient prior to aortic valve replacement surgery. In addition, asymptomatic patients with aortic stenosis should undergo cardiac catherization when echocardiographic findings are inconsistent with the clinical findings[1].
Cardiac Catheterization
Assessment of the Gradient Across the Aortic Valve
- Left heart catheterization is performed to simultaneously assess left ventricular and aortic pressures. A catheter is placed inside the left ventricle, and pressure is simultaneously recorded in the femoral artery. The difference in pressures is the pressure gradient across the aortic valve.
- The femoral pressure is usually measured off of the sidearm of the femoral sheath. The sheath size of the femoral sheath should be at least on French size larger than the catheter so that the catheter does not induce dampening of the pressure waveform in the femoral sheath.
- It is assumed that the femoral blood pressure is equal to the blood pressure in the aorta just distal to the aortic valve. This assumption is often wrong. Prior to crossing the aortic valve, the blood pressure should be compared in the proximal aorta and the femoral sheath. As a result of the reflection of the waveforms in stiff atherosclerotic blood vessel, there may be a higher pressure in the femoral sheath. This is termed femoral augmentation. The augmentation of the femoral blood pressure must be subtracted from the peak gradient in calculating the aortic valve area. On the other hand, the pressure in the femoral artery may be lower than that of the central aorta due to peripheral arterial disease. In this scenario, the femoral pressure must be upwardly adjusted to account for this.
- Fluid dynamic mediated subvalvular pressure gradients are often present in patients with severe aortic stenosis in the absence of an anatomic subvalvular obstruction and constitute ~50% of the total measured transvalvular gradient. The extent of increase in cardiac output during exercise is inversely related to the magnitude of subvalvular gradient.[2]
Assessment of the Aortic Valve Area
- Simultaneous measurement of left ventricular output (measures the flow through the aortic valve) and the pressure gradient across the aortic valve provides the variables that are required to calculate the aortic valve area.[3][4]
- According to the current recommendations, following dobutamine infusion, if the aortic valve area increases to >1.2 cm2, and the mean pressure gradient rises above 30 mmHg, such patients may benefit from aortic valve replacement. Failure to achieve these improvements has shown to be associated with higher early surgical mortality in comparison to patients who can augment their contractility and gradient: 32-33% versus 5-7%, respectively. Additionally, 5-year survival was lower in patients who could not augment their contractility in comparison to those who could: 10–25% versus 88%, respectively.
- Aortic valve area can be calculated by the following two equations:
Gorlin Equation:
Aortic Valve Area (cms2) = (Stroke volume (mL/beat) ÷ Systolic ejection period (secs/beat)) ÷ ( 44.3 x square root of mean systolic pressure gradient between the left ventricle and aorta (mmHg))
Hakki Equation:
Aortic Valve Area (cms2) = (Cardiac output (liters/minute)) ÷ (Square root of mean systolic pressure gradient between the left ventricle and aorta (mmHg))
Assessment of the Aortic Valve Resistance:
- Simultaneous measurement of left ventricular output (measures the flow through the aortic valve) and the pressure gradient across the aortic valve provides the variables that are required to calculate the aortic valve resistance.[5][6]
- Cannon JD Jr et al, described the benefit of calculating aortic valve resistance in conjunction with the Gorlin formula to differentiate patients with true severe aortic stenosis from those with mild aortic stenosis.[7] The clinical implication of this differentiation is that patients with mild aortic stenosis may not benefit from aortic valve replacement.
- Patients with high cardiac output with minimal or no increase in pressure gradient also fall into the category of mild aortic stenosis and may not benefit from aortic valve replacement.
- Furthermore, aortic valve resistance is less flow-dependent than aortic valve area which is of particular benefit in patients with low output aortic stenosis.[7]
Aortic Valve Resistance (dyne seconds per cms5) = { (Mean Pressure Gradient between the left ventricle and aorta (mmHg) x Heart Rate (beats/min) x Systolic ejection period (secs/beat) ) ÷ Cardiac output } x 1.33
- Unsteady fluid-dynamics support the use of aortic valve area calculation over other measures of aortic stenosis including aortic valve resistance.[10][11][12]
Crossing the Stenosed Aortic Valve
- In patients with moderate to severe aortic stenosis, the pigtail catheter will generally not cross the aortic valve in the traditional fashion.
- A straight tipped wire is placed in the catheter.
- In the 30 degree left anterior oblique projection, the wire is then extruded from the pigtail catheter.
- Multiple attempts are made to advance the straight tipped wire across the aortic valve.
- The odds of crossing the valve are improved if you can identify the central jet of blood coming out of the aortic valve. This can be identified by the wire vibrating or shuddering when it is in the jet. The wire should then be advanced in the central region of shuddering or rapid aortic velocity.
- Should the pigtail catheter not provide the appropriate angulation, it can be replaced with a Judkins right 4 catheter (JR4). If this catheter does not work, it can be replaced with an Amplatz right 1 or 2 catheter (AR1 or AR2).
- Care must be taken to heparinize the patient so that a clot does not form on the wire. Alternatively, the wire must be periodically removed and cleared of any clot.
Simultaneous left ventricular and aortic pressure tracings demonstrate a pressure gradient between the left ventricle and aorta, suggesting aortic stenosis. The left ventricle generates higher pressures than what is transmitted to the aorta. The pressure gradient, caused by aortic stenosis, is represented by the green shaded area. (AO = ascending aorta; LV = left ventricle; ECG = electrocardiogram.) The heart may be catheterized to directly measure the pressure on both sides of the aortic valve.
Coronary Angiography
Coronary angiography is performed in elderly patients who are undergoing aortic vavle replacement to ascertain whether obstructive epicardial coronary artery disease is present that would warrant coronary artery bypass graft surgery.
2008 and Incorporated 2006 ACC/AHA Guidelines for the Management of Patients with Valvular Heart Disease (DO NOT EDIT) [1]
Cardiac Catheterization Indications (DO NOT EDIT) [1]
Class I |
"1. Coronary angiography is recommended before aortic valve replacement in patients with AS at risk for CAD.(Level of Evidence: B) " |
"2. Cardiac catheterization for hemodynamic measurements is recommended for assessment of severity of AS in symptomatic patients when noninvasive tests are inconclusive or when there is a discrepancy between noninvasive tests and clinical findings regarding severity of AS. (Level of Evidence: C) " |
"3. Coronary angiography is recommended before aortic valve replacement in patients with AS for whom a pulmonary autograft (Ross procedure) is contemplated and if the origin of the coronary arteries was not identified by noninvasive technique.(Level of Evidence: C) " |
Class III |
"1. Cardiac catheterization for hemodynamic measurements is not recommended for the assessment of severity of AS before aortic valve replacement when noninvasive tests are adequate and concordant with clinical findings.(Level of Evidence: C) " |
"2. Cardiac catheterization for hemodynamic measurements is not recommended for the assessment of LV function and severity of AS in asymptomatic patients. (Level of Evidence: C) " |
Class IIa |
"1. Cardiac catheterization for hemodynamic measurements with infusion of dobutamine can be useful for evaluation of patients with low-flow/low-gradient AS and LV dysfunction. (Level of Evidence: C)" |
Asymptomatic Adolescents (DO NOT EDIT) [1]
Class I |
"1. Cardiac catheterization for the evaluation of AS is an effective diagnostic tool in the asymptomatic adolescent or young adult when results of Doppler echocardiography are equivocal regarding severity of AS or when there is a discrepancy between clinical and noninvasive findings regarding severity of AS. (Level of Evidence: C) " |
"2. Cardiac catheterization is indicated in the adolescent or young adult with AS who has symptoms of angina, syncope, or dyspnea on exertion if the Doppler mean gradient is greater than 30 mm Hg or the peak velocity is greater than 3.5 m per second (peak gradient greater than 50 mm Hg). (Level of Evidence: C) " |
"3. Cardiac catheterization is indicated in the asymptomatic adolescent or young adult with AS who develops T-wave inversion at rest over the left precordium if the Doppler mean gradient is greater than 30 mm Hg or the peak velocity is greater than 3.5 m per second (peak gradient greater than 50 mm Hg).(Level of Evidence: C) " |
Class IIa |
"1. Cardiac catheterization for the evaluation of AS is a reasonable diagnostic tool in the asymptomatic adolescent or young adult who has a Doppler mean gradient greater than 40 mm Hg or a peak velocity greater than 4 m per second (peak gradient greater than 64 mm Hg). (Level of Evidence: C)" |
"2. Cardiac catheterization for the evaluation of AS is reasonable in the adolescent or young adult who has a Doppler mean gradient greater than 30 mm Hg or a peak velocity greater than 3.5 m per second (peak gradient greater than 50 mm Hg) if the patient is interested in athletic participation or becoming pregnant, or if the clinical findings and the Doppler echocardiographic findings are disparate. (Level of Evidence: C)" |
Sources
- 2008 ACC/AHA Guidelines incorporated into the 2006 guidelines for the management of patients with valvular heart disease [1]
References
- ↑ 1.0 1.1 1.2 1.3 1.4 Bonow RO, Carabello BA, Chatterjee K, de Leon AC, Faxon DP, Freed MD; et al. (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.
- ↑ Laskey WK, Kussmaul WG (2001). "Subvalvular gradients in patients with valvular aortic stenosis: prevalence, magnitude, and physiological importance". Circulation. 104 (9): 1019–22. PMID 11524395. Retrieved 2012-04-12. Unknown parameter
|month=
ignored (help) - ↑ Hirshfeld JW, Kolansky DM. Valve function: Stenosis and regurgitation. In: Diagnostic and Therapeutic Cardiac Catheterization, 2nd ed, Pepine CJ, Hill JA, Lambert CR (Eds), Williams & Wilkins, Baltimore 1994. p.443
- ↑ Carabello BA, Grossman W. Calculation of stenotic valve orifice area. In: Cardiac Catheterization and Angiography, 3rd ed, Grossman W (Ed), Lea and Febiger, Philadelphia 1986. p.143.
- ↑ Hirshfeld JW, Kolansky DM. Valve function: Stenosis and regurgitation. In: Diagnostic and Therapeutic Cardiac Catheterization, 2nd ed, Pepine CJ, Hill JA, Lambert CR (Eds), Williams & Wilkins, Baltimore 1994. p.443
- ↑ Carabello BA, Grossman W. Calculation of stenotic valve orifice area. In: Cardiac Catheterization and Angiography, 3rd ed, Grossman W (Ed), Lea and Febiger, Philadelphia 1986. p.143.
- ↑ 7.0 7.1 Cannon JD, Zile MR, Crawford FA, Carabello BA (1992). "Aortic valve resistance as an adjunct to the Gorlin formula in assessing the severity of aortic stenosis in symptomatic patients". Journal of the American College of Cardiology. 20 (7): 1517–23. PMID 1452925. Retrieved 2012-04-12. Unknown parameter
|month=
ignored (help) - ↑ Badano L, Cassottano P, Bertoli D, Carratino L, Lucatti A, Spirito P (1996). "Changes in effective aortic valve area during ejection in adults with aortic stenosis". The American Journal of Cardiology. 78 (9): 1023–8. PMID 8916482. Retrieved 2012-04-12. Unknown parameter
|month=
ignored (help) - ↑ Ford LE, Feldman T, Chiu YC, Carroll JD (1990). "Hemodynamic resistance as a measure of functional impairment in aortic valvular stenosis". Circulation Research. 66 (1): 1–7. PMID 2295132. Retrieved 2012-04-12. Unknown parameter
|month=
ignored (help) - ↑ Bermejo J, Antoranz JC, Burwash IG, Alvarez JL, Moreno M, García-Fernández MA, Otto CM (2002). "In-vivo analysis of the instantaneous transvalvular pressure difference-flow relationship in aortic valve stenosis: implications of unsteady fluid-dynamics for the clinical assessment of disease severity". The Journal of Heart Valve Disease. 11 (4): 557–66. PMID 12150306. Unknown parameter
|month=
ignored (help);|access-date=
requires|url=
(help) - ↑ Kadem L, Rieu R, Dumesnil JG, Durand LG, Pibarot P (2006). "Flow-dependent changes in Doppler-derived aortic valve effective orifice area are real and not due to artifact". Journal of the American College of Cardiology. 47 (1): 131–7. doi:10.1016/j.jacc.2005.05.100. PMID 16386676. Retrieved 2012-04-12. Unknown parameter
|month=
ignored (help) - ↑ Otto CM (2006). "Valvular aortic stenosis: disease severity and timing of intervention". Journal of the American College of Cardiology. 47 (11): 2141–51. doi:10.1016/j.jacc.2006.03.002. PMID 16750677. Retrieved 2012-04-12. Unknown parameter
|month=
ignored (help)
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