CLINICIAN UPDATE
Treatment Options in Severe Aortic Stenosis
Eric R. Bates, MD
C ase presentation: An 80-year-old
woman is referred for cardiovas-
cular evaluation because of a systolic
murmur. She denies symptoms of an-
gina, syncope, or heart failure. The
physical examination and echocardio-
gram are consistent with severe aortic
stenosis (AS). What further evaluation
is indicated?
Aortic stenosis is becoming more
frequent as the average age of the
population increases; it affects up to
5% of the elderly population.1 The
diagnosis of severe AS is most easily
defined by Doppler echocardiography
with maximum aortic jet velocity ⬎4.0
m/s, mean transvalvular pressure gra-
dient ⬎40 mm Hg, and continuity
equation valve area ⬍1.0 cm2 or valve
area index ⬍0.6 cm2 (Figure 1).2 How-
ever, when cardiac output is low, a
lower transvalular gradient and jet ve-
locity may be present. Echocardiogra-
phy is also used in patients with AS to
assess left ventricular hypertrophy,
size, and function; left atrial size, and
the presence of pulmonary hyperten-
sion or other associated valvular dis-
ease. Nevertheless, the decision to pro-
ceed with aortic valve replacement
(AVR) is usually based on the pres-
ence of symptoms. So, if this patient
really is asymptomatic, the echocar-
From the Division of Cardiovascular Diseases, Department of Internal Medicine, University of Michigan, Ann Arbor, MI.
Correspondence to Eric R. Bates, MD, CVC Cardiovascular Medicine, 1500 E. Medical Center Dr, SPC 5869, Ann Arbor, MI 48109-5869. E-mail
ebates@umich.edu
(Circulation. 2011;124:355-359.)
© 2011 American Heart Association, Inc.
Circulation is available at http://circ.ahajournals.org
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diographic criteria for severe AS
would not automatically result in a
cardiac surgery referral.3–5
The 1%/y risk of sudden death in
asymptomatic patients with AS is not
higher than that of historical controls
without AS.5 However, because pa-
tients may deny or fail to recognize
symptoms or avoid them by decreasing
physical activity, exercise testing can
be useful in asymptomatic patients to
confirm that the patient really is symp-
tom free. Exercise-induced symptoms,
ventricular tachycardia, or hypotension
predict a short symptom-free survival
and an increased mortality risk.6,7
Asymptomatic patients with severe AS
not referred for AVR should be mon-
itored frequently for change in exer-
cise tolerance, exertional chest dis-
comfort, dyspnea, lightheadedness, or
syncope. An annual echocardiogram
should be performed to evaluate dis-
ease progression in patients with se-
vere AS. The higher the maximum
aortic jet velocity, the more likely they
are to require AVR within 5 years.3,8
An annual increase in aortic jet veloc-
ity ⬎0.3 m 䡠 second⫺1 䡠 year⫺1 or a
decrease in valve area ⬎0.1 cm2/y
indicates rapid hemodynamic progres-
sion. Concomitant coronary artery dis-
ease or moderate/severe aortic valve
DOI: 10.1161/CIRCULATIONAHA.110.974204
355 by guest on December 6, 2015
calcification are associated with rapid
hemodynamic progression.4 Condi-
tions in which early AVR may be
warranted in the absence of symptoms,
include very severe AS (maximum jet
velocity ⬎5.0 m/s, mean gradient
⬎60 mm Hg, or aortic valve area ⬍0.6
cm2), left ventricular ejection fraction
(LVEF) ⬍ 0.50, abnormal exercise test
result, markedly calcified aortic valve,
rapid progression of AS by Doppler
criteria, or expected delays in the di-
agnosis or treatment of disease pro-
gression.2 Clinical judgment is partic-
ularly required in the elderly to
balance the risk of waiting for disease
progression and operating when the
patient is older versus operating earlier
when surgical risk may be lower.
Medical treatment options are lim-
ited. Systemic arterial hypertension
should be treated cautiously and hypo-
tension avoided. Routine endocarditis
antibiotic prophylaxis is no longer rec-
ommended. Although the active valvu-
lar disease process is characterized by
lipid accumulation, inflammation, and
calcification, statin therapy does not
reduce disease progression in patients
with severe AS.9
Case Presentation, Continued
Two years later, the patient was hos-
pitalized in the cardiac care unit with
356 Circulation July 19, 2011

patients with severe AS and symptoms

is 25%, and average survival is only 2
to 3 years, so the decision to refer
patients for AVR is simple once they
become symptomatic. Aortic valve re-
placement reduces symptoms and im-
proves survival in patients who are not
at high risk for perioperative morbidity
or mortality.15–17 Because of the risk of
sudden death, AVR should be per-
formed promptly after the onset of
symptoms. Age is not a contraindica-
tion for surgery, but comorbid disease
may make surgical risk unacceptable.
Surgical risk can be estimated by
online risk calculators from the Soci-
ety of Thoracic Surgeons (http://www.
Figure 1. Management strategy for patients with severe aortic stenosis. AVA indicates sts.org/quality-research-patient-safety/
aortic valve area; BP, blood pressure; CABG, coronary artery bypass graft surgery; quality/risk-calculator-and-models/
echo, echocardiography; LV, left ventricular; and Vmax, maximal velocity across aortic risk-calculator) or the European System
valve by Doppler echocardiography. Reprinted from Bonow et al2 with permission of the
publisher. Copyright © 2008, the American Heart Association. for Cardiac Operative Risk Evaluation
(EuroSCORE; http://www.euroscore.org).
pulmonary edema. Echocardiography early recoil, restenosis, and the failure The STS score tends to underestimate
demonstrated severe AS, moderate mi- to alter leaflet pathology. Procedural risk for AVR, whereas the logistic
tral regurgitation, and a moderately advances include lower-profile balloon EuroSCORE overestimates risk for
reduced LVEF. Aggressive attempts at catheters, avoidance of double balloon isolated valve surgery.18 Important co-
diuresis did not normalize her volume inflations, balloon sizing based on aor- morbidities not captured include an
status, and renal function declined. tic annular diameter determined by extensively calcified (porcelain) aorta,
echocardiography, rapid ventricular oxygen-dependent respiratory insuffi-
Inoperable Aortic Stenosis pacing for more precise balloon posi- ciency, cirrhosis, history of chest wall
Some patients are inoperable because tioning, and percutaneous suture arte- radiation or deformity, immobility, de-
of clinical status or comorbidities. Bal- rial closure. Complications occur in mentia, and frailty; these will need to
loon aortic valvuloplasty (BAV) 15% to 20% of cases and include be included in the calculation when an
through a retrograde transfemoral ap- aortic regurgitation, stroke, and vascu- AVR risk score is eventually devel-
proach can be used as a bridge to AVR lar injury requiring intervention.11,12 oped. From 1994 to 1999, average
or transcatheter aortic valve implanta- Procedural mortality is 1% to 2%. in-hospital mortality for AVR in pa-
tion in unstable patients with high Long-term survival is not changed by tients ⬎65 years of age was 8.8%
surgical risk to allow for improvement BAV and is ⬇50% at 1 year, 35% at 2 (13.0% in lowest-volume hospitals and
in LVEF, severe mitral regurgitation, years, and 20% at 3 years.13,14 6.0% in highest-volume hospitals).19
pulmonary hypertension, and clinical Recent data from the STS database
status.10 It more commonly is used for Case Presentation, Continued showed an overall in-hospital mortal-
palliation for patients in whom AVR Balloon aortic valvuloplasty was per- ity rate of 2.6% and stroke rate of 1.3%
cannot be performed because of co- formed successfully, renal function for isolated AVR in 2006, reflecting
morbid conditions.11 Contraindications normalized, and the patient subse- important advances in patient selection
include moderate or severe aortic re- quently became euvolemic with fur- and surgical and perioperative treat-
gurgitation, severe peripheral artery ther therapy. After a short stay in a ment.20 Other complications included
disease, and futility. Balloon inflation rehabilitation facility, she was dis- myocardial infarction, bleeding, infec-
stretches the annulus, separates fused charged home and returned 1 month tion, atrial fibrillation, atrioventricular
commissures, and creates microfrac- later to the cardiac surgery clinic for heart block, and acute kidney injury.
tures in calcified nodules. However, evaluation. Risks increase with advanced age, fe-
the procedure results in incomplete male sex, LVEF ⬍30%, congestive
relief of outflow obstruction (increase Surgical Candidates, heart failure, and associated coronary
in valve area by 0.4 cm2, halving of Normal Risk artery disease.
gradient). The small hemodynamic Symptomatic AS is a fatal disease if Surgical options for AS include
benefit only lasts months because of left uncorrected. Annual mortality in AVR with a mechanical or biopros-
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 Bates Treatment Options in Severe Aortic Stenosis 357

receive the benefit of a surgical opin-

ion or a risk score calculation. Ad-
vanced age and left ventricular dys-
function appear to be overstressed by
primary care physicians and general
cardiologists compared with comor-
bidities in subjective clinical decision
making. It is increasingly recognized
that a multidisciplinary evaluation by a
heart team that includes interventional
cardiology, cardiac surgery, anesthesi-
ology, and imaging specialists will im-
prove clinical decision making.

Case Presentation, Continued

The cardiac surgeon reviewed her his-
Figure 2. Examples of surgical replacement aortic valves: A, Aortic homograft. B, Peri- tory, performed a physical examination,
cardial valve. C, Porcine valve. D, Ball-and-cage valve. E, Tilting-disk valve. F, Bileaflet
valve. Reprinted from Chikwe et al 21 with permission of the publisher. Copyright © examined her test results, and explained
2003, MediNews (Cardiology) Ltd. the risks and benefits of AVR. Subse-
quent testing revealed a porcelain aorta
thetic (heterograft) valve, AVR with rioration, symptomatic valve prosthe- and a STS risk score of 15%.
an allograft (homograft) valve, pul- sis–patient mismatch, thrombosis, em-
monic valve autotransplantation (Ross bolism, bleeding complications from Surgical Candidates,
operation), aortic valve repair, and left anticoagulation, endocarditis, tissue High Risk
ventricle–to– descending aorta shunt ingrowth, and hemolysis from Patients may be refused for AVR be-
(Figure 2). Mechanical AVR designs periprosthetic aortic regurgitation. cause of high surgical risk (STS score
include ball-and-cage valves, single ⬎10% or logistic EuroSCORE ⬎20%)
tilting-disc prostheses, and bileaflet Surgical Candidates Not or coexisting noncardiac conditions
prostheses.21 Bioprosthetic AVR can Referred for AVR that predict poor survival potential.
be stented or stentless and are reason- One third of patients with symptomatic Transcatheter valve implantation is in-
able in patients who want to avoid the AS not referred for AVR have accept- tended for symptomatic patients with
risks and inconvenience of anticoagu- able surgical risk on the basis of ob- severe calcific AS requiring AVR who
lation. Bioprosthetic valve durability is jective measures.22–23 This represents a are at high risk for open heart surgery
improving but may not be as good as a major gap between guideline- because of comorbid conditions and
mechanical valve. Prosthetic valve recommended therapy and clinical for patients who are inoperable. The
complications include structural dete- practice.2 Most of these patients do not Edwards SAPIEN valve system (Ed-
wards Lifesciences Inc, Irvine, CA) is
a trileaflet bovine pericardial valve
mounted on a balloon-expandable
stainless steel stent (Figure 3A). The
second generation Edwards Sapien XT
valve is mounted on a cobalt chro-
mium stent frame. The CoreValve sys-
tem (Medtronic, Minneapolis, MN) is
a trileaflet porcine pericardial valve
mounted in a self-expanding nitinol
stent (Figure 3B). The devices are
usually implanted by a transfemoral
retrograde approach; the alternative is
a transapical approach for the SAPIEN
valve and a subclavian approach for
the CoreValve. The devices are not
approved for use in the United States
Figure 3. Examples of transcatheter replacement aortic valves: A, SAPIEN valve and
balloon-expandable delivery system. B, CoreValve and self-expandable (unsheathed) but have been commercially available
delivery system. in Europe since 2007.
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358 Circulation July 19, 2011
Exclusion criteria include bicuspid
or noncalcified aortic valve, peripheral
vascular or aorta disease, coronary ar-
tery disease requiring revasculariza-
tion, severe chronic kidney disease,
severe left ventricular hypertrophy,
LVEF ⬍20%, severe mitral regurgita-
tion, or significant neurological dis-
ease. Procedural success rates are
⬎90%. On average, the aortic valve
gradient decreases from ⬇45 to
10 mm Hg, and the aortic valve area
increases from 0.7 cm2 to 1.7 cm2. In
the Placement of Aortic Transcatheter
Valves (PARTNER) trial,24 1-year
mortality in inoperable patients com-
pared with standard therapy (BAV in
84%) was reduced from 50.7% to
30.7%. Procedural complications in-
clude death (2% to 5%), stroke (2% to
5%), acute kidney injury (1% to 2%),
coronary occlusion (0.6%), major
bleeding (15%), vascular access site
complications (10% to 15%), need for
permanent pacemaker (5% to 15%),
significant perivalvular leak (10%),
valve embolization (0.3%), and pro-
tracted hospitalization. Thirty-day
mortality is 6% to 10%, and 1-year
mortality is 20% to 30%. Long-term
outcomes reflect patient risk rather
than procedural risk. Results will im-
prove with better operator experience,
improved devices, refined patient se-
lection, and inclusion of lower-risk
patients.
Future technical developments will
include reduced device profile; better
ways of measuring anatomic valve,
aortic root, and peripheral artery di-
mensions; completely repositionable
and retrievable devices; better percuta-
neous closure systems; and improved
device durability. Cerebral protection
devices delivered through the radial
artery are in development.25 More ob-
servational studies will be needed to
improve patient selection and assess
safety and durability. The potential of
percutaneous valve-in-valve replace-
ment may expand the use of biopros-
thetic valves in younger patients.26
Conclusion
Severe AS is a fatal disease if left
uncorrected. Balloon aortic valvulo-
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plasty can be used as a bridge to
therapy in unstable patients or for pal-
liation when valve replacement is not
possible. Surgical AVR is the treat-
ment of choice. Transcatheter valve
implantation is an alternative for se-
lected high-risk surgical or inoperable
patients but is available in the United
States only through clinical trials.
Case Presentation, Conclusion
The patient was felt to be a candidate
for transcatheter aortic valve implanta-
tion and was offered participation in a
randomized, clinical trial at another
medical center developing a structural
heart disease program. She elected to
travel to a high-volume experienced
European center for further treatment.
Disclosures
None.
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 Treatment Options in Severe Aortic Stenosis
Eric R. Bates

Circulation. 2011;124:355-359
doi: 10.1161/CIRCULATIONAHA.110.974204
Circulation is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231
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