2009 12 08 aortic valve disease - dr. stultzdrstultz.com/presentations/2009 12 08 aortic...

Aortic Valve DiseaseAortic Valve DiseaseIllustrative CasesIllustrative Cases

December 8, 2009December 8, 2009

David Stultz, MD, FACCDavid Stultz, MD, FACC

Southwest Cardiology, IncSouthwest Cardiology, Inc

Handout available at http://www.drstultz.com

© 2009 David Stultz, MD

DisclosuresDisclosures

Nothing to discloseNothing to disclose


ObjectivesObjectives

Understand the use of echocardiographyUnderstand the use of echocardiographyto assess aortic valve diseaseto assess aortic valve disease

Apply clinical guidelines to managementApply clinical guidelines to managementof aortic valve diseaseof aortic valve disease


Aortic Valve AnatomyAortic Valve Anatomy

Hurst 12th ed.


Selected Abnormalities of Aortic ValveSelected Abnormalities of Aortic Valve

Aortic StenosisAortic Stenosis

–– Narrowing of the valve orificeNarrowing of the valve orifice

Aortic RegurgitationAortic Regurgitation

–– Incompetence of the valveIncompetence of the valve

–– BloodBlood ““leaksleaks”” from aorta to left ventricle infrom aorta to left ventricle inventricular diastoleventricular diastole

Bicuspid Aortic ValveBicuspid Aortic Valve

EndocarditisEndocarditis


How to Assess the Aortic ValveHow to Assess the Aortic Valve

Clinical HistoryClinical History

Physical ExaminationPhysical Examination

EchocardiographyEchocardiography

–– TransthoracicTransthoracic

–– TransesophagealTransesophageal

AngiographyAngiography

Cardiac CT (not regurgitation, though)Cardiac CT (not regurgitation, though)

MRIMRI


Why do aortic valves becomeWhy do aortic valves becomestenoticstenotic??

Valvular StenosisValvular Stenosis–– Bicuspid valve with calcificationBicuspid valve with calcification

–– AgeAge--relatedrelated calcificcalcific aortic stenosisaortic stenosis

–– RheumaticRheumatic

–– Rare causes: Congenital, Rheumatoid, SevereRare causes: Congenital, Rheumatoid, Severeatherosclerosis (Hyperlipidemia),atherosclerosis (Hyperlipidemia), alkaptonuriaalkaptonuria

SupravalvularSupravalvular StenosisStenosis

SubvalvularSubvalvular StenosisStenosis–– DiscreteDiscrete

–– Hypertrophic CardiomyopathyHypertrophic Cardiomyopathy

Braunwald 8th ed.


Normal aortic valve Bicuspid aortic stenosis

Rheumatic aortic stenosis Age related aortic stenosis

Braunwald 8th ed.


How to assess aortic stenosis by echoHow to assess aortic stenosis by echo

22--D echoD echo

–– PlanimetryPlanimetry –– measure the valve orificemeasure the valve orifice

Doppler HemodynamicsDoppler Hemodynamics

–– Continuity equationContinuity equation

–– Peak/Mean pressure gradientPeak/Mean pressure gradient


PlanimetryPlanimetry

Technically difficult, may overestimate valve areaTechnically difficult, may overestimate valve area

Transthoracic Transesophageal


Echo DopplerEcho Doppler

Echo probe generates sound waveEcho probe generates sound wave

Sound wave reflects off tissue/bloodSound wave reflects off tissue/blood

Echo probe has a time window to listenEcho probe has a time window to listenfor these reflectionsfor these reflections

Moving targets (blood) will create aMoving targets (blood) will create afrequency shift in the sound wavefrequency shift in the sound wave

This frequency shift can be translated intoThis frequency shift can be translated intoa velocitya velocity

Can measure the velocity of blood flowCan measure the velocity of blood flow


Continuity equationContinuity equation

Without a nozzle, theWithout a nozzle, thewater velocity insidewater velocity insidethe hose (1/2the hose (1/2””) is the) is thesame as after thesame as after thehosehose



With a nozzle, the water velocityWith a nozzle, the water velocityinside the hose (1/2inside the hose (1/2””) is lower) is lowerthan after the nozzlethan after the nozzle

Nozzle reduces the orifice areaNozzle reduces the orifice area

Know diameter of hose (1/2Know diameter of hose (1/2””))

Can measure velocity of water in theCan measure velocity of water in thehosehose

Can measure the velocity of waterCan measure the velocity of waterafter the nozzleafter the nozzle

What is the effective orifice createdWhat is the effective orifice createdby the nozzle?by the nozzle?


Conservation of massConservation of mass

Flow before nozzle = Flow after nozzleFlow before nozzle = Flow after nozzle

Area of hose * velocity of water in hose =Area of hose * velocity of water in hose =Orifice area * velocity of water after hoseOrifice area * velocity of water after hose

–– Area = (Area = (½½ * diameter)* diameter)22 * 3.14(* 3.14(ππ))

Can solve equation for orifice areaCan solve equation for orifice area




Now think of the aortic valveNow think of the aortic valve

Can measure LVOT diameterCan measure LVOT diameter

Can measure LVOT velocity (or TVI)Can measure LVOT velocity (or TVI)

Can measure velocity (or TVI) after aortic valveCan measure velocity (or TVI) after aortic valve

Can solve for aortic valve orificeCan solve for aortic valve orifice

Simplified Bernoulli equationSimplified Bernoulli equation

–– 4v4v22 = mmHg pressure gradient= mmHg pressure gradient


Case 1Case 1

77 year old African American Male77 year old African American Male

Referred for evaluation of murmurReferred for evaluation of murmur

Medical history: HTNMedical history: HTN

Asymptomatic, able to walk up and downAsymptomatic, able to walk up and downstairs, shovel snowstairs, shovel snow

BP 146/86BP 146/86

Crescendo/Crescendo/DescrescendoDescrescendo 3/6 systolic3/6 systolicmurmur at left lowermurmur at left lower sternalsternal borderborder


Severe aortic stenosisSevere aortic stenosis

Aortic valve area <1.0cmAortic valve area <1.0cm22

Peak aortic velocity >4.0mPeak aortic velocity >4.0m22

Mean aortic valve gradient >40 mmHgMean aortic valve gradient >40 mmHg


Pathphysiology of Aortic StenosisPathphysiology of Aortic Stenosis

Previously felt to occur as a normalPreviously felt to occur as a normalprocess of aging, related toprocess of aging, related to mechnicalmechnicalstress on normal valvestress on normal valve

Current theory involves inflammatoryCurrent theory involves inflammatoryprocess with T lymphocyte andprocess with T lymphocyte andmacrophage infiltration with lipidmacrophage infiltration with lipidaccumulation, resulting in bone formationaccumulation, resulting in bone formation(calcification)(calcification)

Braunwald 8th ed.


Prevalence of Aortic StenosisPrevalence of Aortic Stenosis

At age 65At age 65

–– 29% have aortic sclerosis29% have aortic sclerosis

Irregular thickening of leafletsIrregular thickening of leaflets

Mild/early form of stenosisMild/early form of stenosis

–– 2% have aortic stenosis2% have aortic stenosis

Braunwald 8th ed.


Risk factors for ASRisk factors for AS

GeneticGenetic –– familial clustering noted infamilial clustering noted insome casessome cases

Elevated LDLElevated LDL

ElevatedElevated Lp(aLp(a))

DiabetesDiabetes

SmokingSmoking

HypertensionHypertension

Braunwald 8th ed.


Pathphysiology of Aortic StenosisPathphysiology of Aortic Stenosis

Valve orifice area slowly declines overValve orifice area slowly declines overtimetime

Symptoms progress graduallySymptoms progress gradually

LV pressure overload results inLV pressure overload results inconcentric hypertrophyconcentric hypertrophy

Increased LV wall mass, diastolicIncreased LV wall mass, diastolicdysfunctiondysfunction

Braunwald 8th ed.


Symptoms of AS (Severe)Symptoms of AS (Severe)

Exertional Dyspnea/Heart failureExertional Dyspnea/Heart failure

Chest painChest pain

–– 50% with significant coronary atherosclerosis50% with significant coronary atherosclerosis

SyncopeSyncope

–– Vasodilation with fixed cardiac outputVasodilation with fixed cardiac output


Physical Examination of ASPhysical Examination of AS

Palpation of the carotid upstrokePalpation of the carotid upstroke–– ParvusParvus etet tardustardus

Systolic murmurSystolic murmur–– CrescendoCrescendo--decrescendodecrescendo

Heart failureHeart failure–– Crackles in lung fieldsCrackles in lung fields

–– Jugular venous distensionJugular venous distension

–– EdemaEdema


Management of AsymptomaticManagement of AsymptomaticSevere Aortic StenosisSevere Aortic Stenosis

Up to 33% remain asymptomatic for 5Up to 33% remain asymptomatic for 5yearsyears

Without symptoms, prognosis is generallyWithout symptoms, prognosis is generallygoodgood–– Risk of sudden death 1Risk of sudden death 1--2%/year2%/year

Consider exercise testing under directConsider exercise testing under directcardiologist supervisioncardiologist supervision–– VerifyVerify ““asymptomaticasymptomatic””

–– Assess for fall in blood pressureAssess for fall in blood pressure

Pellikka PA, Sarano ME, Nishimura RA, et al. Outcome of 622 adults with asymptomatic, hemodynamically significant aortic stenosisduring prolonged follow-up. Circulation 2005;111:3290 –5.Rafique AM, Biner S, Ray I, Forrester JS, Tolstrup K, Siegel RJ. Meta-analysis of prognostic value of stress testing in patients withasymptomatic severe aortic stenosis. Am J Cardiol. 2009 Oct 1;104(7):972-7.


Does statin treatment affect AS?Does statin treatment affect AS?

Retrospective studies show slowing ofRetrospective studies show slowing ofprogressionprogression

Prospective (Prospective (atorvastatinatorvastatin) study showed no) study showed nobenefit in advancedbenefit in advanced calcificcalcific aortic stenosisaortic stenosis

Prospective (Prospective (rosuvastatinrosuvastatin) study showed) study showedslowing of progression in less severe aorticslowing of progression in less severe aortic

stenosisstenosis

Ongoing prospective trial usingOngoing prospective trial using ezetimideezetimide ((ZetiaZetia))

Cowell SJ, Newby DE, Prescott RJ, et al: A randomized trial of intensive lipid-lowering therapy in calcificaortic stenosis. N Engl J Med 2005; 352:2389.Moura LM, Ramos SF, Zamorano JL, et al: Rosuvastatin Affective Aortic Valve Endothelium to slow theprogression of aortic stenosis. J Am Coll Cardiol 2007; 49:554.


Case 1 managementCase 1 management

Exercised for 9 minutes on treadmillExercised for 9 minutes on treadmill

–– Manual modified protocolManual modified protocol

–– 6.8 METS6.8 METS

–– 83% maximum predicted heart rate83% maximum predicted heart rate

–– Good rise in blood pressureGood rise in blood pressure

–– Mild shortness of breath symptomsMild shortness of breath symptoms

Started on Beta blockerStarted on Beta blocker


Case 1 PlanCase 1 Plan

Remains asymptomatic 1 year laterRemains asymptomatic 1 year later

Plan for clinical followPlan for clinical follow--up every 6 monthsup every 6 months

If other heart surgery (CABG) indicated,If other heart surgery (CABG) indicated,valve will be replacedvalve will be replaced


Case 2Case 2

48 year old male48 year old male

Heart murmur appreciated on physicalHeart murmur appreciated on physicalexaminationexamination

Mild shortness of breath with exertionMild shortness of breath with exertion

–– Climbing 3 flights of stairsClimbing 3 flights of stairs

–– No Chest painNo Chest pain

Overweight, quit smoking recentlyOverweight, quit smoking recently

DM, HTN, HLPDM, HTN, HLP


Bicuspid Aortic ValveBicuspid Aortic Valve

Moderate to severe aortic stenosisModerate to severe aortic stenosis

–– Aortic valve area 1.1 cmAortic valve area 1.1 cm22

–– Mean pressure gradient 44.5 mmHgMean pressure gradient 44.5 mmHg

–– Peak velocity 4.4Peak velocity 4.4 m/sm/s

Mild aortic valve regurgitationMild aortic valve regurgitation

Dilated of aortic root (4.3 cm)Dilated of aortic root (4.3 cm)


Bicuspid aortic valveBicuspid aortic valve

11--2% Incidence in live births2% Incidence in live births

Male predominance (up to 80%)Male predominance (up to 80%)

Association with disorders of aortaAssociation with disorders of aorta

–– CoarctationCoarctation

–– DilitationDilitation/aneurysm/aneurysm

–– DissectionDissection

Symptomatic stenosis develops around age 50Symptomatic stenosis develops around age 50

Familial form with autosomal dominantFamilial form with autosomal dominantinheritance (NOTCH1 gene mutation)inheritance (NOTCH1 gene mutation)

Carabello BA, Paulus WJ. Aortic stenosis. Lancet. 2009 Mar 14;373(9667):956-66. Epub 2009 Feb 21.Braunwald 8th ed.


Management of ModerateManagement of ModerateBicuspid Aortic StenosisBicuspid Aortic Stenosis

If there is aortic dilatation (>4.0cm)If there is aortic dilatation (>4.0cm)

–– Beta Blockers unless contraindicatedBeta Blockers unless contraindicated

Moderate to severe regurgitationModerate to severe regurgitation

–– Echo every yearEcho every year

–– Surgery if aortic root >5.0cm or >0.5cm/1Surgery if aortic root >5.0cm or >0.5cm/1yearyear

Without aortic dilatationWithout aortic dilatation

–– No specific medical therapyNo specific medical therapy

–– Echo every 1Echo every 1--2 years or if clinical change2 years or if clinical changeBonow RO, Carabello BA, Chatterjee K, de Leon A C Jr, Faxon DP, Freed MD, Gaasch WH, Lytle BW, Nishimura RA, O'Gara PT, O'Rourke RA, Otto CM, Shah

PM, Shanew ise JS; American College of Cardiology/American Heart Association Task Force on Practice Guidelines. 2008 focused update incorporated into theACC/A HA 2006 guidelines for the management of patients w ith valvular heart disease: a report of the American College of Cardiology/Amer ican HeartAssociation Task Force on Practice Guidelines (Writing Committee to revise the 1998 guidelines for the management of patients w ith valvular heart disease).Endorsed by the Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. J

Am Coll Cardiol. 2008 Sep 23;52(13):e1-142


Case 2 plan of careCase 2 plan of care

On statin forOn statin for hyperlipidemiahyperlipidemia

Treatment of DM, HTN (ARB)Treatment of DM, HTN (ARB)

Aspirin 81mg dailyAspirin 81mg daily

FollowupFollowup office and echo in 6 monthsoffice and echo in 6 months


Case 3Case 3

44 year old white male44 year old white male

Referred for loud murmurReferred for loud murmur

Spouse started hearing his heart at nightSpouse started hearing his heart at nightabout 1 month agoabout 1 month ago

Asymptomatic, physically active, able toAsymptomatic, physically active, able toclimb stairsclimb stairs

No smoking, DM, HTNNo smoking, DM, HTN

6/6 loud6/6 loud holodiastolicholodiastolic murmurmurmur


Indications for Valve replacementIndications for Valve replacementin Aortic regurgitationin Aortic regurgitation

Connective tissue disease with aortic rootConnective tissue disease with aortic rootdilitationdilitation (25%)(25%)

Congenital, including bicuspid (13%)Congenital, including bicuspid (13%)

Infective endocarditis (10%)Infective endocarditis (10%)

AgeAge--relatedrelated calcificcalcific degeneration (7%)degeneration (7%)

Other/Unknown/Idiopathic (35%)Other/Unknown/Idiopathic (35%)–– Trauma, rheumatic,Trauma, rheumatic, syphillissyphillis, aortic, aortic

dissection,dissection, fenfluraminefenfluramine ++ phenterminephentermine,,Antiphospholipid syndromeAntiphospholipid syndrome

Crawford & DiMarco, 2nd edBorer JS, Hochreiter C, Herrold EM, Supino P, Aschermann M, Wencker D, Devereux RB, Roman MJ, Szulc M, Kligfield P, IsomOW. Prediction of indications for valve replacement among asymptomatic or minimally symptomatic patients with chronic aorticregurgitation and normal left ventricular performance. Circulation. 1998 Feb 17;97(6):525-34.


How to assess aortic regurgitationHow to assess aortic regurgitation

HistoryHistory

PhysicalPhysical

EchocardiogramEchocardiogram

AngiographyAngiography

MRIMRI


EchocardiographicEchocardiographic evaluation ofevaluation ofaortic regurgitationaortic regurgitation

Color DopplerColor Doppler–– Jet areaJet area–– Jet heightJet height

–– PISA EROPISA ERO

PressurePressure ½½ timetimeRegurgitantRegurgitant fraction, volumefraction, volumeDescending thoracic aortic flow reversalDescending thoracic aortic flow reversal

Left ventricular EF and dimensionsLeft ventricular EF and dimensionsNo single criteria is perfectNo single criteria is perfectEccentric jets are oftenEccentric jets are often worseworse thanthancalculated/estimatedcalculated/estimated


ColorColor dopplerdoppler

Feigenbaum 6th ed

Mild Moderate Severe

Visual inspectionVisual inspection

Also Jet area and jet heightAlso Jet area and jet height


PressurePressure ½½ timetime–– Measurement of time it takes for aorticMeasurement of time it takes for aortic

pressure to equalize to (pressure to equalize to (½½) left ventricular) left ventricular

pressurepressure

–– Variable thresholds in literature!Variable thresholds in literature!

<300ms consistent with severe regurgitation<300ms consistent with severe regurgitation

300300--500ms moderate500ms moderate

>500ms mild>500ms mild


Flow reversal in descendingFlow reversal in descendingthoracic aortathoracic aorta


Case 3 managementCase 3 management

SevereSevere posteriorlyposteriorly eccentric aortic regurgitationeccentric aortic regurgitationLV diastolic dimension 6.9cmLV diastolic dimension 6.9cmEF 60EF 60--65%65%

No clear etiologyNo clear etiologyBlood cultures obtainedBlood cultures obtained–– 2 of 2 initially positive gram +2 of 2 initially positive gram + coccicocci

–– 1 of 4 subsequently positive gram +1 of 4 subsequently positive gram + coccicocci–– Initially admitted, treated with IV antibioticsInitially admitted, treated with IV antibiotics–– Blood cultures staph, all different speciesBlood cultures staph, all different species

–– Antibiotics stopped, no symptomsAntibiotics stopped, no symptoms


Criteria for Surgery?Criteria for Surgery?

Asymptomatic Severe Aortic regurgitationAsymptomatic Severe Aortic regurgitation

–– EF <50%EF <50%

–– Systolic dimension >5.5cmSystolic dimension >5.5cm

–– Diastolic dimension >7.5cmDiastolic dimension >7.5cm

Guidelines are complicated, but becomeGuidelines are complicated, but becomemore vigilant about surveillance whenmore vigilant about surveillance when

–– Systolic dimension >5.0cmSystolic dimension >5.0cm

–– Diastolic dimension >7.0cmDiastolic dimension >7.0cm


Issues not addressed in guidelinesIssues not addressed in guidelines

NoncoronaryNoncoronary cuspcusp prolapseprolapse with severewith severeeccentric jet hitting anterior leaflet of theeccentric jet hitting anterior leaflet of themitral valvemitral valve

–– ? Possibility to distort Mitral valve architecture? Possibility to distort Mitral valve architecture

Unclear etiologyUnclear etiology

LifestyleLifestyle

–– Both patient and spouse hear the murmurBoth patient and spouse hear the murmur


Referred for elective surgeryReferred for elective surgery

Mechanical orMechanical or bioprostheticbioprosthetic valve?valve?

IntraoperativelyIntraoperatively, torn, torn noncoronarynoncoronary cuspcuspnotednoted

Overall stable postoperative courseOverall stable postoperative course


Case 4Case 4

Male in mid 40Male in mid 40’’ss

History of automobile accident withHistory of automobile accident withorthopedic traumaorthopedic trauma

Several years afterward, noted to haveSeveral years afterward, noted to havemurmurmurmur

Echo showed aortic regurgitationEcho showed aortic regurgitation

Overall asymptomaticOverall asymptomatic

Does not want to take medicationsDoes not want to take medications


ManagementManagement

LV diastolic dimension 7.6cmLV diastolic dimension 7.6cm

EF 55EF 55--60%60%

Class 2A indication for surgery by guidelinesClass 2A indication for surgery by guidelines

Vasodilator therapy (Vasodilator therapy (NifedipineNifedipine, ACE inhibitors), ACE inhibitors)are a Class 2B indicationare a Class 2B indication

Pt declines surgery and medicationsPt declines surgery and medications

66--12 month clinical and echo12 month clinical and echo followupfollowup

Bonow RO, Carabello BA, Chatterjee K, de Leon A C Jr, Faxon DP, Freed MD, Gaasch WH, Lytle BW, Nishimura RA, O'Gara PT, O'Rourke RA, Otto CM, Shah




As time passesAs time passes……

InitialInitial 5 Years Later5 Years Later

LVH decreasesLV diastolic dimension decreases




Pressure ½ Time decreasesCorrelating with worse regurgitation


Variable natural historyVariable natural history

Asymptomatic patients with normal LV functionAsymptomatic patients with normal LV function–– <6%/year have symptoms and/or LV dysfunction<6%/year have symptoms and/or LV dysfunction

–– <3.5%/year progress to asymptomatic LV dysfunction<3.5%/year progress to asymptomatic LV dysfunction

–– <0.2%/year have sudden cardiac death<0.2%/year have sudden cardiac death

Asymptomatic patients with LV dysfunctionAsymptomatic patients with LV dysfunction–– >25%/year progress to have symptoms>25%/year progress to have symptoms

Symptomatic Severe Aortic RegurgitationSymptomatic Severe Aortic Regurgitation–– >10%/year mortality rate>10%/year mortality rate

Bonow RO, Carabello BA, Chatterjee K, de Leon A C Jr, Faxon DP, Freed MD, Gaasch WH, Lytle BW, Nishimura RA, O'Gara PT, O'Rourke RA, Otto CM, Shah




ConclusionConclusion

Case illustrations of decision making forCase illustrations of decision making for

–– Asymptomatic severe aortic stenosisAsymptomatic severe aortic stenosis

–– Moderate bicuspid aortic stenosis with aortic rootModerate bicuspid aortic stenosis with aortic rootdilatationdilatation

–– Asymptomatic severe aortic regurgitationAsymptomatic severe aortic regurgitation

Symptoms + Severe AS or AR = SurgerySymptoms + Severe AS or AR = Surgery

No clear medical managementNo clear medical management

–– Consider Beta blockers for aortic root dilatationConsider Beta blockers for aortic root dilatation

–– StatinsStatins for mildfor mild--moderate aortic stenosis?moderate aortic stenosis?


ReferencesReferences

Bonow RO, Carabello BA, Chatterjee K, de Leon AC Jr, Faxon DP, Freed MD, Gaasch WH, Lytle BW, Nishimura RA,O'Gara PT, O'Rourke RA, Otto CM, Shah PM, Shanewise JS; American College of Cardiology/American HeartAssociation Task Force on Practice Guidelines. 2008 focused update incorporated into the ACC/AHA 2006guidelines for the management of patients with valvular heart disease: a report of the American College ofCardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to revise the 1998guidelines for the management of patients with valvular heart disease). Endorsed by the Society of CardiovascularAnesthesiologists, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. JAm Coll Cardiol. 2008 Sep 23;52(13):e1-142.

Borer JS, Hochreiter C, Herrold EM, Supino P, Aschermann M, Wencker D, Devereux RB, Roman MJ, Szulc M, KligfieldP, Isom OW. Prediction of indications for valve replacement among asymptomatic or minimally symptomaticpatients with chronic aortic regurgitation and normal left ventricular performance. Circulation. 1998 Feb17;97(6):525-34.

Cowell SJ, Newby DE, Prescott RJ, et al: A randomized trial of intensive lipid-lowering therapy in calcific aortic stenosis.N Engl J Med 2005; 352:2389.

Moura LM, Ramos SF, Zamorano JL, et al: Rosuvastatin Affective Aortic Valve Endothelium to slow the progression ofaortic stenosis. J Am Coll Cardiol 2007; 49:554.

Pellikka PA, Sarano ME, Nishimura RA, et al. Outcome of 622 adults with asymptomatic, hemodynamically significantaortic stenosis during prolonged follow-up. Circulation 2005;111:3290 –5.

Rafique AM, Biner S, Ray I, Forrester JS, Tolstrup K, Siegel RJ. Meta-analysis of prognostic value of stress testing inpatients with asymptomatic severe aortic stenosis. Am J Cardiol. 2009 Oct 1;104(7):972-7.


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