Download Asymptomatic Aortic Stenosis in the Elderly A Clinical Review

Clinical Review & Education
Clinical Crossroads
Asymptomatic Aortic Stenosis in the Elderly
A Clinical Review
Warren J. Manning, MD
IMPORTANCE Aortic stenosis is the most common form of valvular heart disease. Progression
of aortic stenosis is very slow and highly variable. Decisions about when to perform valve
surgery are made by subjective assessment of patient symptoms and objective measures of
the valve and ventricular function by transthoracic echocardiography.
CME Quiz at
jamanetworkcme.com and
CME Questions 1500
OBJECTIVE To review current concepts regarding the development, progression, and
assessment of aortic stenosis; the appropriate monitoring intervals for transthoracic
echocardiography; and the indications for valve procedures.
EVIDENCE REVIEW Guidelines and literature search.
FINDINGS Angina, exertional syncope, and heart failure are key symptoms indicating a need
for intervention. The frequency of valvular monitoring by transthoracic echocardiography is
guided by the disease severity. Despite evidence of severe disease, valve procedures can
safely be deferred if patients experience no symptoms and have normal left ventricular
ejection fraction. Asymptomatic patients with severe aortic stenosis may subconsciously
curtail their activities to avoid symptoms. Apparently, asymptomatic patients can undergo a
carefully monitored exercise stress test to confirm both their asymptomatic status and
hemodynamic response to exercise. Bioprosthetic valves are a good replacement alternative
for older patients who are good surgical candidates and who have no need for warfarin
therapy. For patients who are at high or very high risk of cardiac surgery, transcutaneous
aortic valve implantation is an increasing available and preferred over medical
management.
CONCLUSIONS AND RELEVANCE Asymptomatic patients with severe aortic stenosis require
frequent monitoring of their subjective symptoms combined with objective measurement of
aortic valve gradient and ventricular function by transthoracic echocardiography. Although
conventional surgical replacement remains the mainstay of therapy for aortic stenosis,
transcutaneous aortic valve implantation options are evolving.
JAMA. 2013;310(14):1490-1497. doi:10.1001/jama.2013.279194
This article is based on a conference that took place at the Medicine Grand
Rounds at Beth Israel Deaconess Medical Center, Boston, Massachusetts, on
March 12, 2009.
Case Presentation
Dr Libman Dr T is an 85-year-old physician with a history of hypertension and aortic stenosis who was in his usual state of health until
2 months ago, when he noticed mild shortness of breath while walking up an incline. Symptoms did not progress and were inconsistent. He was able to walk on level surfaces and pursue his normal
daily activities without difficulty. He denied chest pain, orthopnea,
paroxysmal nocturnal dyspnea, peripheral edema, lightheadedness, or syncope. He has no history of coronary artery disease. His
1490
Author Affiliation: Cardiovascular
Division, Department of Medicine,
and Department of Radiology, Beth
Israel Deaconess Medical Center,
Harvard Medical School, Boston,
Massachusetts.
Corresponding Author: Warren J.
Manning, MD, Cardiovascular
Division, 330 Brookline Ave, Boston,
MA 02215 ([email protected]).
Section Editor: Edward H.
Livingston, MD, Deputy Editor, JAMA.
past medical history is noteworthy for recurrent skin cancers, restless leg syndrome, chronic constipation, and hyperlipidemia.
His current medications include 50 mg of hydrochlorothiazide, 40 mg of lisinopril, 0.25 mg of pramipexole, and 20 mg of simvastatin daily and 50 mg of metoprolol tartrate twice daily.
Dr T is married and lives with his wife. He has 2 grown children.
He is a semiretired allergist-immunologist. He has 1 to 2 glasses of
wine per week. He has no history of cigarette smoking.
On examination, his blood pressure was 124/78 mm Hg with a
regular pulse of 64/min. Jugular venous pressure was 6 cm; carotid
arteries were palpable with slightly delayed upstroke and no bruits.
His heart beat at a regular rhythm with normal S1, fixed split S2, and
no S3 or S4. There was a grade 3/4 systolic ejection murmur, which
was loudest at his right upper sternal border radiating toward the
carotids. The point of maximal impulse was not displaced.
JAMA October 9, 2013 Volume 310, Number 14
Downloaded From: http://jama.jamanetwork.com/ by a Beth Israel Deaconess Medical Center User on 09/24/2014
jama.com
Asymptomatic Aortic Stenosis in the Elderly
Clinical Crossroads Clinical Review & Education
Figure 1. Dr T's Transthoracic Echocardiogram Continuous Wave Color Doppler Results, August 2008 and January 2009
A August 2008
B January 2009
Aortic valve area
Aortic valve peak velocity
Aoritc valve peak gradient
Aortic valve mean gradient
0.9 cm2
4.1 m/s
67 mm Hg
43 mm Hg
A transthoracic echocardiograph, performed 2 months prior,
showed mild concentric left ventricular (LV) hypertrophy with normal cavity size and normal regional-global systolic function (ejection fraction, >60%; normal ejection fraction, 55%-70%). Peak gradient across the aortic valve was 97 mm Hg (normal peak gradient,
<15 mm Hg), and a calculated aortic valve area of 0.7 cm2 (normal
aortic valve area, >3.0 cm2). There was no aortic regurgitation. There
was mild mitral regurgitation. Seven months before, his peak gradient was 67 mm Hg, demonstrating that the severity of aortic stenosis had increased (Figure 1).
A stress nuclear study a month prior was stopped after 6.75 minutes of a modified Bruce protocol due to fatigue and an asymptomatic reduction in blood pressure from 148/84 mm Hg to 122/68 mm
Hg. Electrocardiograph showed 2 to 2.5 mm of upslopinghorizontal ST segment depression inferolaterally, which became
downsloping in recovery. The nuclear study was interpreted as “probably normal myocardial perfusion.”
Dr T was diagnosed with severe aortic stenosis. In light of his
ability to function well and in the absence of rest symptoms or reduction in LV function, it was decided to monitor him clinically for
the present time.
Dr T: His View
I was diagnosed with a heart murmur, which was compatible with
aortic stenosis about 8 or 10 years ago. I was asymptomatic at that
time. The first symptom I had was this past summer, when I was
climbing a steep hill to my summer house. I noticed that I was getting extraordinarily short of breath. I continue, however, to go to the
gym at least 3 times a week and work out for 20 to 30 minutes on
elliptical machines without symptoms. I talked to my primary care
jama.com
Aortic valve area
Aortic valve peak velocity
Aoritc valve peak gradient
Aortic valve mean gradient
0.7 cm2
4.9 m/s
97 mm Hg
68 mm Hg
physician who suggested that we get another echocardiograph,
which showed severe aortic stenosis.
I was obviously concerned. I live a very active lifestyle for someone
who is 85. I see patients on a part time basis, go to school, and live actively. I am concerned that at some point, I will become symptomatic,
and then I will have to get a valve replacement. I know that my doctors
havesuggestedwatchfulwaiting,butIamwonderinggivenmyageand
generally good health whether I should proceed with surgery now.
Epidemiology and Etiology of Aortic Stenosis
Dr Manning Dr T is a relatively active 85-year-old gentleman who
shares a valvular pathology with many older adults. He is fortunate
tohavelivedtoanerainwhichnoninvasiveimagingtechnologyisreadily available both to diagnose and to monitor this common disorder.
In addition, highly successful treatment options are widely available.
Given the increase in longevity afforded by other advances in health
care, degenerative calcified aortic stenosis has now become the most
common form of valvular heart disease in the Western World with a
prevalence of 3% of those 75 years or older, and representing a major health care burden that is projected to increase with an aging
population.1 There is ongoing basic science and clinical research to further our understanding of its pathogenesis and management.2
Although we often think of aortic stenosis as fixed obstructive
aortic valve disease, a similar presentation, albeit in a younger population, may occur with supravalvular and subvalvular membranes.
These “nonvalvular but fixed” obstructive conditions may present
in a similar manner and are readily distinguished by transthoracic echocardiography.
Aortic stenosis is characterized by a progressive narrowing of
the aortic valve that leads to a pressure overload state on the LV. ValJAMA October 9, 2013 Volume 310, Number 14
Downloaded From: http://jama.jamanetwork.com/ by a Beth Israel Deaconess Medical Center User on 09/24/2014
1491
Clinical Review & Education Clinical Crossroads
Asymptomatic Aortic Stenosis in the Elderly
Figure 2. Normal and Stenotic Aortic Valve Morphologies
A Normal heart valve anatomy
B
Examples of types of aortic stenosis and age of presentation of aortic stenosis
ANTERIOR
Left coronary
artery (LCA)
Right coronary
artery (RCA)
PULMONARY
VA LV E
Degenerative calcific aortic stenosis
(elderly [>70 yrs])
LCA
Aortic valve
Rheumatic aortic stenosis
(young and middle-aged adults)
LCA
RCA
RCA
Valve area
LEF T
ATRIOVENTRICULAR
VALVE
RIGHT
ATRIOVENTRICULAR
VALVE
Bicuspid aortic stenosis
(young and middle-aged adultsa)
LCA
RCA
Unicuspid aortic stenosis
(infants and children)
LCA
RCA
Coronary sinus
POSTERIOR
a
Most common congenital cardiac anomaly in adults (men > women)1; also occurs secondary to thoracic aorta anomalies (aneurysm, dissection, or coarctation)
vular aortic stenosis has several etiologies that typically present in
different age groups, including unicuspid, bicuspid, and trileaflet aortic stenosis (Figure 2). Rheumatic aortic stenosis leads to leaflet thickening and fusion with a progressively narrow, “oval” residual orifice. Patients with degenerative calcific aortic stenosis are typically
older (>70 years), and the residual orifice retains a Y or branch opening configuration. The pathophysiology of degenerative calcific
aortic stenosis is not a passive process reflecting the inevitable consequence of aging but is the result of a biologically active process
with characteristic features of an osteoblast phenotype.3 Risk factors for disease progression mirror those of coronary artery disease. Of those risk factors, Dr T has advanced age, hypertension, and
hyperlipidemia.4 Other risk factors include diabetes, smoking, and
renal dysfunction. An inflammatory basis for aortic stenosis is supported by studies demonstrating increasing 18-fluorodeoxyglucose levels, a positron emission tomographic ligand marker of macrophage activity, with increasing valve stenosis severity.5
Symptoms and Signs
An increase in the aortic valve gradient results in pressure overload and
concentric LV wall thickening or hypertrophy with preservation of LV
cavitysizeandejectionfraction—aswasseeninDrT’stransthoracicechocardiograph. Despite a preserved ejection fraction, subclinical abnormalitiesofsystolicfunctionmaybepresentandidentifiedbyassessment
of LV strain.6,7 The hypertrophy and associated fibrosis8 likely contributes to LV diastolic dysfunction and increased filling pressure. In a subset of patients with severe aortic stenosis, LV hypertrophy is absent.9
The 3 cardinal symptoms of aortic stenosis indicating a need for
mechanical intervention are angina, exertional syncope or presyncope, and heart failure (eg, exertional cardiac dyspnea, orthopnea,
1492
paroxysmal nocturnal dyspnea, pedal edema). Heart failure is the
result of LV hypertrophy with fibrosis8 and diastolic dysfunction, with
increased filling pressure, often despite preserved LV ejection fraction; exertional syncope or presyncope is the result of peripheral vasodilation with an inability of the heart to increase stroke volume;
and angina is the result of increased myocardial muscle and increased myocardial demand with limited coronary blood supply without or with obstructive coronary artery disease. Exertional angina
may be present in up to 50% of patients with aortic stenosis despite the absence of obstructive coronary artery disease.10
Physical examination findings include a delayed carotid upstroke
(pulsus parvus et tardus or slowly rising carotid upstroke; a finding that
is often absent in older persons) and a sustained point of maximal impulse due to LV hypertrophy. Auscultation demonstrates a normal or
accentuated S1, followed by a harsh, late-peaking systolic murmur (an
exampleofthesoundisavailableathttp://www.dundee.ac.uk/medther
/Cardiology/as.htm) that is best heard in the right or left upper sternal
border and is transmitted to the right clavicular area and carotids (compared with the murmur of mitral regurgitation that is best heard at the
left lower sternal border, peaks earlier, and radiates to the axilla and
back). As the severity of aortic stenosis progresses, the murmur peaks
later in systole or may even decrease in intensity as stroke volume declines. The aortic component of S2 is soft or absent in severe aortic stenosis. Although I have not had the opportunity to examine Dr T, I suspect the aortic valve closure component of S2 was minimal or absent.
Criteria for Climactically Significant Aortic Stenosis
The normal aortic valve has 3 thin, highly mobile leaflets that provide a valve opening of 3 to 4 cm2 and minimal gradient (<10 mm
Hg). Progression of aortic stenosis in the early stages is very slow,
JAMA October 9, 2013 Volume 310, Number 14
Downloaded From: http://jama.jamanetwork.com/ by a Beth Israel Deaconess Medical Center User on 09/24/2014
jama.com
Asymptomatic Aortic Stenosis in the Elderly
Clinical Crossroads Clinical Review & Education
Table 1. Clinical Data From Serial Echocardiographic Studies Performed on Dr T
Peak velocity, m/s
March 18, 2003
3.4
September 19,
2005
3.3
August 6, 2008
4.1
January 21, 2009
4.9
Gradient, mm Hg
Peak
46
Mean
26
Valve area, cm2
44
1.0
with estimates of lumen loss of 0.10 cm2 per year11 and increase in
peak gradient of 10 mm Hg per year,12 but there is great variation
among individual patients. There is considerable valve area reserve. Symptoms of aortic stenosis do not develop until there has
been 60% to 75% loss of valve area to less than 1.0 cm2. As a result
of this large reserve and very slow progression, many patients remain asymptomatic for a decade or more, though a murmur is usually heard when the valve area is 1.5 to 2 cm2, a level considered to
be mild aortic stenosis. As expected, normalization for body size may
be more meaningful, especially for larger or smaller individuals—
with severe aortic stenosis defined as a valve area of less than 1.0
cm2 or a body surface area normalized valve area of less than 0.6
cm2/m2. Dr T has a valve area of 0.7 cm2 (0.35 cm2/m2) placing him
in the range of severe aortic stenosis.
Measurement of Aortic Stenosis
Patients with a suspicion of aortic stenosis or with heart failure and
exertional syncope will benefit from a resting transthoracic echocardiography, which readily allows for assessment of LV wall thickness (for hypertrophy), cavity size, and regional-global systolic function. In addition, aortic valve morphology (number of leaflets, leaflet
thickening, leaflet mobility) can be assessed. Finally, Doppler echocardiography allows for an accurate noninvasive assessment of aortic valve peak and mean gradients, estimation of aortic valve area,
and assessment of aortic regurgitation and mitral regurgitation.
Using continuous wave Doppler, the peak and mean gradients
across the stenotic aortic valve can be measured. The transthoracic
echocardiography peak aortic valve gradient is slightly higher than
the gradient reported at cardiac catheterization as the transthoracic echocardiography Doppler gradient measures the maximal instantaneous peak gradient between the aorta and the LV, while invasive measurements report the difference between the peak LV
pressure and the peak aortic pressure (Figure 1). The mean gradients derived by both methods are similar.
If Doppler echocardiography is unable to assess the valve, other
options include planimetry using moderately invasive 2- or 3-dimensional transesophageal echocardiography, computed
tomography,13 and cardiovascular magnetic resonance.14 All of these
methods offer good correlation with transthoracic echocardiography and cardiac catheterization but with additional cost, invasiveness, or radiation exposure. They are infrequently needed.
Medical Management of Significant Aortic Stenosis
Dr T has been monitored for nearly a decade since his initial diagnosis with minimal change in the peak aortic valve gradient from
jama.com
67
97
43
68
0.9
0.7
2003 to 2005 but has experienced marked increase between 2005
and 2008 and again between 2008 and 2009 (Table 1). Progression of aortic stenosis is highly variable, but usually is very slow,11,12
and there is tremendous reserve so that symptoms may not develop for many decades or until 75% of the valve area has been lost.
Although overall progression is approximately 0.10 cm2 per year, data
suggest that aortic valve calcification is among the strongest predictors of rapid progression.12
Medical therapy to prevent progression or complications of aortic stenosis is limited. Retrospective data initially suggested a benefit of statin therapy15 in slowing progression, but subsequent prospective studies have demonstrated no benefit for aortic stenosis
disease progression (velocity gradient or progression to aortic valve
replacement).16,17 Prospective studies of statins did demonstrate a
decrease in ischemic cardiovascular events,16 and there is frequent
coexistant coronary artery disease. Due to this benefit, I prescribe
statin therapy for my patients with aortic stenosis, as was done for
Dr T.
Patients with all types of prosthetic valves should received antibiotic prophylaxis,18 but current American Heart Association and
American College of Cardiology (AHA/ACC) prophylaxis recommendations no longer include antibiotic prophylaxis for native valve aortic stenosis (Box 1).18 I advise patients with severe aortic stenosis to
stay well hydrated and to avoid hot tubs or baths, steam rooms, and
saunas so as to avoid hypotension that may result from peripheral
vasodilation with impaired stroke volume augmentation.
For asymptomatic patients with preserved LV ejection fraction, follow-up transthoracic echocardiographs to monitor the gradient and LV systolic function is recommended every 3 to 5 years
for mild aortic stenosis, every 1 to 2 years for moderate aortic stenosis, every 6 to 12 months for asymptomatic severe aortic
stenosis.19,20 Transthoracic echocardiography is performed to monitor both the severity of aortic stenosis and associated aortic regurgitation as well as LV ejection fraction. Dr T has had several transthoracic echocardiographies (Table 1) over the years, demonstrating
relatively stable peak gradients until last year; with subsequent rapid
peak gradient progression from 67 to 97 mm Hg. All of his transthoracic echocardiographies have demonstrated a preserved LV ejection fraction.
Surgical Treatment of Significant Aortic Stenosis
Class I indications for aortic valve surgery as recommended by both
the ACC/AHA and the European Society of Cardiology and European Association for Cardio-Thoracic Surgery (ESC/EACTS)
guidelines20,21 include symptomatic (heart failure, exertional presyncope or syncope, or exertional angina) patients with severe aortic stenosis (aortic valve area, <1.0 cm2 or <0.6 cm2/m2) and asympJAMA October 9, 2013 Volume 310, Number 14
Downloaded From: http://jama.jamanetwork.com/ by a Beth Israel Deaconess Medical Center User on 09/24/2014
1493
Clinical Review & Education Clinical Crossroads
Asymptomatic Aortic Stenosis in the Elderly
Box 1. Recommendations for Patients With Valve Replacements
Box 2. Recommendations for Surgery
Medical therapy
Surgery
Statins
Nonemergency surgery should be performed 4 to 8 weeks after development of symptoms.
Endocarditis prophylaxis is not recommended
Follow-up
Asymptomatic patients with preserved LV ejection fraction
Mild aortic stenosis transthoracic echocardiograph every 3 to 5 years
Moderate aortic stenosis transthoracic echocardiograph every 1 to
2 years
Severe aortic stenosis transthoracic echocardiograph every 6 months
to a year
Symptomatic patients and asymptomatic patients with depressed LV
ejection fraction are referred for coronary angiography and elective
surgery
Finally, aortic valve surgery is recommended (class IIa) for asymptomatic patients with mild or greater aortic stenosis at the time of
coronary artery bypass graft surgery or other heart valve or thoracic
aorta surgery (eg, mitral valve surgery).
Observation
In the absence of symptoms and with preserved left ventricle (LV)
systolic function, observation with deferral of surgery has an excellent prognosis, especially if the peak aortic stenosis gradient is less
than 80 mm Hg.40
Asymptomatic patients with severe aortic stenosis but depressed LV
ejection fraction are also class I surgical candidates.20,21
Table 2. Indications for Aortic Valve Replacement Based on Current Recommendations
Indication for Aortic Valve Replacement
ACC/AHA
Classa
Level of
Evidenceb
ESC/EACTS
Classa
Level of
Evidenceb
Symptomatic severe aortic stenosis
I
B
I
B
Undergoing coronary artery bypass graft
surgery
I
C
I
C
Undergoing surgery on the aorta or other
heart valves
I
C
I
C
a
Not due to another cause.
And left ventricular systolic dysfunction
<0.50c
I
C
I
C
b
Based on the ACC/AHA20 and
ESC/EACTs21 guidelines.
IIa
B
IIa
C
c
Abnormal response to exercise
IIb
C
IIa
C
When the aortic valve is 0.6 cm2,
the mean gradient is higher than 60
mm Hg, and peak velocity is less
than 5 m/s indicates that expected
operative mortality is less than
1.0%.
High likelihood of rapid progression
IIb
C
d
Peak velocity is greater than 5.5 m/s
or progression is greater than 0.3
m/s per year.
Severe aortic stenosis
Moderate aortic stenosis undergoing coronary
artery bypass graft surgery, surgery on the
aorta, or surgery on the other heart valve
Abbreviations: ACC/AHA, American
College of Cardiology and American
Heart Association; ESC/EACTS,
European Society of Cardiology and
European Association for
Cardio-Thoracic Surgery.
Asymptomatic aortic stenosis
Severe
Extreme severe
b
IIb
C
tomatic patients with depressed ejection fraction (<50%; Box 2).
Of the 3 cardinal symptoms, heart failure is the most ominous with
survival of less than a year after heart failure symptoms without valve
replacement.22 For patients who present with exertional syncope,
survival is less than 2 years after development of syncope without
valve replacement (Table 2, Figure 3).
Dr T is largely asymptomatic except for a single episode of dyspnea while walking up a steep incline. He reports being able to perform his usual daily activities, including regular use of elliptical machines without symptoms. Some patients will subconsciously restrict
their activity to avoid symptoms. Thus, while they have no symptoms, it is because they have curtailed their activities, often ascribing their diminished activity level to “advancing age.” For patients
with equivocal symptoms like Dr T, I often perform a carefully monitored exercise stress test. An abnormal response (found in a third
of seemingly asymptomatic patients) includes the development of
symptoms or a decrease in blood pressure and defines a high-risk
group that is likely to need valve replacement within a year.23 Dr T’s
stress test showed a drop in blood pressure and ischemic ST-wave
depression suggesting that he is at high risk of mortality (Box 3).
Conventional aortic stenosis treatment options include surgical valve replacement with a mechanical or bioprosthetic valve, a
1494
IIa
d
C
cadaver aortic valve, and the Ross procedure (Table 3). A new
option for high-risk patients is transcutaneous aortic valve
implant.25-27 Both mechanical and bioprosthetic aortic valves give a
similar hemodynamic profile. All prosthetic valves increase the risk
of endocarditis, so antibiotic prophylaxis is recommended.
Mechanical aortic valves are more durable but have higher thrombogenicity, requiring lifelong warfarin (typical target international
normalized ratio, 2.0-3.0). Oral warfarin alternatives including dabigatran, rivaroxaban, and apixaban have not been fully assessed for
mechanical valves, but adverse events have been reported for
dabigatran.28 A prospective trial comparing dabigatran with warfarin in patients with prosthetic valves was prematurely stopped due
to increased stroke, myocardial infarction, and mechanical valve
thrombi in the dabigatran group.29 Bioprosthetic aortic valves do
not require warfarin, but they are less durable,30 especially in
younger patients and those with renal dysfunction, failing due to
fibrosis or calcification with resultant stenosis, or regurgitation, or
both. The longevity of bioprosthetic valves is inversely related to
the patient’s age, with a longevity of 1 to 2 decades for patients
older than 70 years vs 5 to 10 years for patients younger than 50
years. Thus, otherwise healthy patients younger than 60 years or
patients who need long-term warfarin for another condition
JAMA October 9, 2013 Volume 310, Number 14
Downloaded From: http://jama.jamanetwork.com/ by a Beth Israel Deaconess Medical Center User on 09/24/2014
jama.com
Asymptomatic Aortic Stenosis in the Elderly
(eg, atrial fibrillation) generally receive mechanical valves, while for
those older than 70 years old, such as Dr T, bioprosthetic valves are
preferred. These bioprostheses will provide a good hemodynamic
result with 15- to 20-year longevity.
In-hospital mortality among patients requiring isolated aortic
valve surgery is 2% to 5% and increases to 5% to 10% if coronary
artery bypass graft surgery is also needed.31 Excellent results are obtained even among patients like Dr T who are older than 80 years.32
Risk factors for in-hospital mortality include hypertension, diabetes, depressed LV ejection fraction, emergency surgery, and prior
cardiac surgery.31-33 From these data, Dr T has a predicted inhospital mortality of approximately 3% with excellent long-term
survival.31-33 For patients who survive without morbidity, the longterm prognosis of isolated aortic valve replacement for aortic stenosis is excellent and approximates the normal population.34 Adverse long-term risk factors include stroke, smoking, diabetes, and
renal failure.32,35
Were Dr T to have numerous comorbidities so as to be at very
high risk of cardiac surgery, consideration of transcutaneous aortic
valve implant would be considered. In the United States, the
Edwards Sapien and Medtronic CoreValve options have been the
most widely studied. Current data are promising in very high-risk
patients with regards to short-term morbidity and mortality with
benefit at 2 years for mortality (vs medical therapy).25-27 Major
advantages of the transcutaneous aortic valve implant approach
are the rapid patient recovery but with an increased risk of vascular
complications, heart block, and stroke. Postprocedure aortic regurgitation appears to be a predictor for adverse outcomes.35 Currently, the Edwards Sapien valve is approved by the US Food and
Drug Administration for use in patients with severe symptomatic
calcified aortic stenosis at high risk of operative morbidity and
mortality.36 Data suggest similar 30-day and 1-year mortality and
major morbidity for the Edwards Sapien and Medtronic CoreValve
systems.37
Because the presence of angina may be related to aortic stenosis or coexistant coronary artery disease and because patients with
aortic stenosis are often older with typical risk factors for coronary
artery disease, screening coronary angiography is recommended for
most adult patients prior to aortic valve surgery.20,21 Data suggest
a potential role for coronary computed tomography as a screening
test to exclude obstructive coronary artery disease38 in middleaged patients. If any stenoses are suggested, a coronary angiogram is performed.
Clinical Crossroads Clinical Review & Education
Figure 3. Algorithm for Management of Severe Aortic Stenosis
Follow-up
every 6-12 mo
Severe aortic valve stenosis
Valve area < 1.0 cm2
Indexed valve area < 0.6 cm2/m2 BSA
Yes
Symptoms present or needs
other heart or aortic surgery
No
Uncertain
Symptoms
or
Decrease in BP
Exercise test
No symptoms
or
Increase in BP
Yes
LVEF < 50% ?
No
Aortic valve replacement
Adapted from Bonow et al20 and Vahanian et al.21 BP indicates blood pressure
and LVEF, left ventricular ejection fraction
Box 3. American Heart Association Recommendationsa
I. Evidence or general agreement that a given procedure or treatment is useful and effective.
II. Conflicting evidence or a divergence of opinion about the usefulness or efficacy of a procedure or treatment
a. Evidence favors an interventions usefulness
b. Evidence regarding an interventions utility is less well established
III. Evidence, general agreement, or both that the procedure or treatment is not useful or effective and in some cases may be harmful
a
Based on Gibbons et al.24
Table 3. Treatment Options for Aortic Stenosis
Option
Target Group
Advantages
All
Decrease in ischemic
cardiovascular events
Cadaver
Younger adults
No need for warfarin;
moderate longevity; can
be used for women of
child-bearing age
Biological
>65 y
No need for warfarin;
15-20 year longevity
Medical treatment
Statin
Surgery options
Valve
Recommendations for Dr T
Dr T is relatively asymptomatic but has severe aortic stenosis and
preserved LV ejection fraction. Although he reports regular exercise on an elliptical, I am particularly concerned by the abnormal hypotensive response on stress testing at a low workload, with accompanying ischemic electrocardiographic changes. Based on this,
he has a class IIa recommendation for surgical intervention
(Table 2).20,21 I recommend that he undergo a coronary angiogram
to determine the presence of coexistant coronary artery disease
(there is no need to cross the aortic valve to confirm the gradient or
to perform left ventriculography) followed by elective aortic valve
surgery with a bioprosthetic valve (coronary artery bypass may be
jama.com
Mechanical
<65 y
Needs warfarin
Ross procedurea
<40 y
No need for warfarin;
moderate longevity
TAVI
>65 y
Shorter surgical recovery
Abbreviation: TAVI, transcutaneous aortic valve implant.
a
Ross procedure is an operation in which the patient’s native pulmonic valve is
moved to the aortic position and a cadaver valve is placed in the pulmonic
position.
JAMA October 9, 2013 Volume 310, Number 14
Downloaded From: http://jama.jamanetwork.com/ by a Beth Israel Deaconess Medical Center User on 09/24/2014
1495
Clinical Review & Education Clinical Crossroads
Asymptomatic Aortic Stenosis in the Elderly
needed as well depending on the results of the angiogram). A bioprosthesis will provide good valve longevity without the need for
long-term warfarin. The procedure should be performed in the next
4 to 8 weeks.
Follow-up With Dr T
Based on the recommendations of Dr Manning, Dr T decided to undergo surgery. In April 2009, 1 month after the conference, he underwent coronary angiography. The aortic valve was not crossed with
a catheter. Angiography demonstrated 90% stenoses of the first and
second obtuse marginal arteries. Three weeks later, he underwent
uncomplicated aortic valve replacement with a bioprosthetic valve
and 2-vessel bypass. He was discharged on postoperative day 6 with
home visiting nurse and physical therapy supports.
In 2013, Dr T has just turned 90 years-old and is doing quite well.
He remains happy with his decision to proceed with surgery. He continues to be very physically active, exercising on the elliptical machine every other day without any shortness of breath or chest pain.
He is currently taking 81 mg of aspirin, 2.5 mg of lisinopril, and 20
mg of simvastatin daily and 100 mg of metoprolol succinate twice
a day. He is grateful to Dr Manning for helping him make the decision to proceed with surgery.
Questions and Discussion
QUESTION He has restless leg syndrome that can be caused by iron
deficiency. Do you think he is having intravascular red cell lysis from
the deformed valve?
DR MANNING Although reported, it is not common to have red cell
lysis with native valve aortic stenosis. This condition is more common with prosthetic valve dysfunction either due to a stenosis or a
perivalvular leak. Aortic stenosis has been associated with both angiodysplasia and clotting abnormalities (impaired platelet function
and decreased levels of von Willebrand factors).39
QUESTION Why is it that he can do the elliptical but not walk up
the hill?
DR MANNING I suspect he has modified his activity. We know that
his blood pressure fell at a treadmill speed of only 1.7 miles per hour
and at a 10° elevation. That is not a very high intensity. We also know
that his rate-pressure-product (peak heart rate × peak systolic blood
pressure) only reached 12 000. Even though he is using the elliptical, I suspect it is not with great intensity. Patients with aortic stenosis will often have shortness of breath with exertion and will reduce their effort. They say, “Oh, I’m just getting a little older,” or “I
now prefer doubles to singles tennis.” They are simply adapting to
the inability to increase stroke volume and cardiac output.
QUESTION How do you evaluate patients after surgery? Do they
need yearly echoes?
DR MANNING I usually obtain 1 transthoracic echocardiograph in
the first few months after surgery to document the baseline gradient and any potential valvular regurgitation. Presuming the patient
is stable and asymptomatic, unless there is a change in examination or symptoms, I will not obtain another one for 4 to 5 years.19
Due to the potential for valve failure with bioprosthetic valves, beginning at 10 years after implantation,30 I usually obtain a transthoracic echocardiograph every 3 years.19
ARTICLE INFORMATION
REFERENCES
Conflict of Interest Disclosures: The author has
completed and submitted the ICMJE Form for
Disclosure of Potential Conflicts of Interest and
reports that he has received a research grant from
Philips Medical Systems. Several years after this
presentation, Dr Manning became a site
coinvestigator for the Medtronic CoreValve System
and has received travel reimbursement for an
investigator meeting.
1. Nkomo VT, Gardin JM, Skelton TN, Gottdiener JS,
Scott CG, Enriquez-Sarano M. Burden of valvular
heart diseases: a population-based study. Lancet.
2006;368(9540):1005-1011.
The conference on which this article is based
took place at the Medicine Grand Rounds at Beth
Israel Deaconess Medical Center, Boston,
Massachusetts, on Thursday, March 12, 2009.
3. Rajamannan NM, Subramaniam M, Rickard D,
et al. Human aortic valve calcification is associated
with an osteoblast phenotype. Circulation.
2003;107(17):2181-2184.
Additional Contributions: We thank the patient for
sharing his story and for providing permission to
publish it.
4. Stewart BF, Siscovick D, Lind BK, et al. Clinical
factors associated with calcific aortic valve disease:
Cardiovascular Health Study. J Am Coll Cardiol.
1997;29(3):630-634.
Clinical Crossroads at Beth Israel Deaconess
Medical Center is produced and edited by Risa B.
Burns, MD, series editor; Jon Crocker, MD, Howard
Libman, MD, Eileen E. Reynolds, MD, Amy N. Ship,
MD, Gerald Smetana, MD, and Anjala V. Tess, MD.
1496
QUESTION What is the best way to get Dr T back up on his feet
quickly after surgery?
DR MANNING Prior to surgery, Dr T should stay active to avoid deconditioning by walking and using his elliptical machine but should
not increase his exercise intensity. Preoperative dental assessment
is important to reduce the risk of subsequent endocarditis. Hospitalization would likely be for 5 to 7 days followed by 1 to 2 weeks of
more intense rehabilitation. Near complete recovery is within 2
months, although I advise very active patients after sternotomy to
avoid vigorous upper body exercises (eg, golf, tennis, bowling) for
3 to 6 months to allow for full sternal healing. Walking is an excellent form of postsurgery exercise.
2. NHLBI Works Group Calcific Aortic Stenosis
Executive Summary. National Heart, Lung, and
Blood Institute. http://www.nhlbi.nih.gov/meetings
/workshops/cas.htm. Updated March 2010.
Accessed August 28, 2013.
5. Dweck MR, Jones C, Joshi NV, et al. Assessment
of valvular calcification and inflammation by
positron emission tomography in patients with
aortic stenosis. Circulation. 2012;125(1):76-86.
6. Lancellotti P, Moonen M, Magne J, et al.
Prognostic effect of long-axis left ventricular
dysfunction and B-type natriuretic peptide levels in
asymptomatic aortic stenosis. Am J Cardiol.
2010;105(3):383-388.
7. Bauer F, Mghaieth F, Dervaux N, et al.
Preoperative tissue Doppler imaging differentiates
beneficial from detrimental left ventricular
hypertrophy in patients with surgical aortic
stenosis: a postoperative morbidity study. Heart.
2008;94(11):1440-1445.
8. Azevedo CF, Nigri M, Higuchi ML, et al.
Prognostic significance of myocardial fibrosis
quantification by histopathology and magnetic
resonance imaging in patients with severe aortic
valve disease. J Am Coll Cardiol. 2010;56(4):
278-287.
9. Kupari M, Turto H, Lommi J. Left ventricular
hypertrophy in aortic valve stenosis: preventive or
promotive of systolic dysfunction and heart failure?
Eur Heart J. 2005;26(17):1790-1796.
10. Exadactylos N, Sugrue DD, Oakley CM.
Prevalence of coronary artery disease in patients
JAMA October 9, 2013 Volume 310, Number 14
Downloaded From: http://jama.jamanetwork.com/ by a Beth Israel Deaconess Medical Center User on 09/24/2014
jama.com
Asymptomatic Aortic Stenosis in the Elderly
with isolated aortic valve stenosis. Br Heart J.
1984;51(2):121-124.
11. Palta S, Pai AM, Gill KS, Pai RG. New insights into
the progression of aortic stenosis: implications for
secondary prevention. Circulation.
2000;101(21):2497-2502.
12. Davies SW, Gershlick AH, Balcon R. Progression
of valvar aortic stenosis: a long-term retrospective
study. Eur Heart J. 1991;12(1):10-14.
13. Feuchtner GM, Müller S, Bonatti J, et al.
Sixty-four slice CT evaluation of aortic stenosis
using planimetry of the aortic valve area. AJR Am J
Roentgenol. 2007;189(1):197-203.
14. Debl K, Djavidani B, Seitz J, et al. Planimetry of
aortic valve area in aortic stenosis by magnetic
resonance imaging. Invest Radiol.
2005;40(10):631-636.
15. Bellamy MF, Pellikka PA, Klarich KW, Tajik AJ,
Enriquez-Sarano M. Association of cholesterol
levels, hydroxymethylglutaryl coenzyme-A
reductase inhibitor treatment, and progression of
aortic stenosis in the community. J Am Coll Cardiol.
2002;40(10):1723-1730.
16. Rossebø AB, Pedersen TR, Boman K, et al; SEAS
Investigators. Intensive lipid lowering with
simvastatin and ezetimibe in aortic stenosis. N Engl
J Med. 2008;359(13):1343-1356.
17. Cowell SJ, Newby DE, Prescott RJ, et al; Scottish
Aortic Stenosis and Lipid Lowering Trial, Impact on
Regression (SALTIRE) Investigators. A randomized
trial of intensive lipid-lowering therapy in calcific
aortic stenosis. N Engl J Med. 2005;352(23):23892397.
18. Wilson W, Taubert KA, Gewitz M, et al;
American Heart Association Rheumatic Fever,
Endocarditis, and Kawasaki Disease Committee;
American Heart Association Council on
Cardiovascular Disease in the Young; American
Heart Association Council on Clinical Cardiology;
American Heart Association Council on
Cardiovascular Surgery and Anesthesia; Quality of
Care and Outcomes Research Interdisciplinary
Working Group. Prevention of infective
endocarditis: guidelines from the American Heart
Association: a guideline from the American Heart
Association Rheumatic Fever, Endocarditis, and
Kawasaki Disease Committee, Council on
Cardiovascular Disease in the Young, and the
Council on Clinical Cardiology, Council on
Cardiovascular Surgery and Anesthesia, and the
Quality of Care and Outcomes Research
Interdisciplinary Working Group. Circulation.
2007;116(15):1736-1754.
19. Douglas PS, Garcia MJ, Haines DE, et al;
American College of Cardiology Foundation
Appropriate Use Criteria Task Force; American
Society of Echocardiography; American Heart
Association; American Society of Nuclear
Cardiology; Heart Failure Society of America; Heart
Rhythm Society; Society for Cardiovascular
Angiography and Interventions; Society of Critical
Care Medicine; Society of Cardiovascular Computed
Tomography; Society for Cardiovascular Magnetic
Resonance. ACCF/ASE/AHA/ASNC/HFSA/HRS/
jama.com
Clinical Crossroads Clinical Review & Education
SCAI/SCCM/SCCT/SCMR 2011 Appropriate Use
Criteria for Echocardiography: a report of the
American College of Cardiology Foundation
Appropriate Use Criteria Task Force, American
Society of Echocardiography, American Heart
Association, American Society of Nuclear
Cardiology, Heart Failure Society of America, Heart
Rhythm Society, Society for Cardiovascular
Angiography and Interventions, Society of Critical
Care Medicine, Society of Cardiovascular Computed
Tomography, and Society for Cardiovascular
Magnetic Resonance Endorsed by the American
College of Chest Physicians. J Am Coll Cardiol.
2011;57(9):1126-1166.
20. Bonow RO, Carabello BA, Chaterjee K, et al;
2006 Writing Committee Members; American
College of Cardiology/American Heart Association
Task Force. 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. Circulation.
2008;118:e523-e661.
21. Vahanian A, Alfieri O, Andreotti F, et al; Joint
Task Force on the Management of Valvular Heart
Disease of the European Society of Cardiology
(ESC); European Association for Cardio-Thoracic
Surgery (EACTS). Guidelines on the management of
valvular heart disease (version 2012). Eur Heart J.
2012;33(19):2451-2496.
22. Ross J Jr, Braunwald E. Aortic stenosis.
Circulation. 1968;38(1)(suppl):61-67.
23. Rafique AM, Biner S, Ray I, Forrester JS,
Tolstrup K, Siegel RJ. Meta-analysis of prognostic
value of stress testing in patients with
asymptomatic severe aortic stenosis. Am J Cardiol.
2009;104(7):972-977.
24. Gibbons RJ, Smith S, Antman E; American
College of Cardiology; American Heart Association.
American College of Cardiology/American Heart
Association clinical practice guidelines, I: where do
they come from? Circulation. 2003;107(23):29792986.
25. Rodés-Cabau J, Webb JG, Cheung A, et al.
Long-term outcomes after transcatheter aortic
valve implantation: insights on prognostic factors
and valve durability from the Canadian multicenter
experience. J Am Coll Cardiol. 2012;60(19):18641875.
26. Leon MB, Smith CR, Mack M, et al; PARTNER
Trial Investigators. Transcatheter aortic-valve
implantation for aortic stenosis in patients who
cannot undergo surgery. N Engl J Med.
2010;363(17):1597-1607.
27. Makkar RR, Fontana GP, Jilaihawi H, et al;
PARTNER Trial Investigators. Transcatheter
aortic-valve replacement for inoperable severe
aortic stenosis. N Engl J Med. 2012;366(18):16961704.
28. Price J, Hynes M, Labinaz M, Ruel M,
Boodhwani M. Mechanical valve thrombosis with
dabigatran. J Am Coll Cardiol. 2012;60(17):1710-1711.
29. Pracaxa (dabigatran etexilate mesylate) should
not be used in patients with mechanical prosthetic
heart valves: safety announcement. US Food and
Drug Administration; December 19, 2012.
http://www.fda.gov/Drugs/DrugSafety
/ucm332912.htm. Accessed August 27, 2013.
30. Hammermeister K, Sethi GK, Henderson WG,
Grover FL, Oprian C, Rahimtoola SH. Outcomes 15
years after valve replacement with a mechanical
versus a bioprosthetic valve: final report of the
Veterans Affairs randomized trial. J Am Coll Cardiol.
2000;36(4):1152-1158.
31. Ambler G, Omar RZ, Royston P, Kinsman R,
Keogh BE, Taylor KM. Generic, simple risk
stratification model for heart valve surgery.
Circulation. 2005;112(2):224-231.
32. Vasques F, Messori A, Lucenteforte E, Biancari
F. Immediate and late outcome of patients aged 80
years and older undergoing isolated aortic valve
replacement: a systematic review and
meta-analysis of 48 studies. Am Heart J.
2012;163(3):477-485.
33. The Society of Thoracic Surgeons online STS
risk calculator. http://riskcalc.sts.org
/STSWebRiskCalc273. Accessed August 27, 2013.
34. Kvidal P, Bergström R, Hörte LG, Ståhle E.
Observed and relative survival after aortic valve
replacement. J Am Coll Cardiol. 2000;35(3):
747-756.
35. Kodali SK, Williams MR, Smith CR, et al;
PARTNER Trial Investigators. Two-year outcomes
after transcatheter or surgical aortic-valve
replacement. N Engl J Med. 2012;366(18):16861695.
36. Foreman C to Mazzarella J. October 19, 2012.
US Food and Drug Administration, Silver Spring,
MD. http://www.accessdata.fda.gov/cdrh_docs
/pdf11/p110021a.pdf Accessed August 27, 2013.
37. Chieffo A, Buchanan GL, Van Mieghem NM,
et al. Transcatheter aortic valve implantation with
the Edwards SAPIEN versus the Medtronic
CoreValve Revalving system devices: a multicenter
collaborative study: the PRAGMATIC Plus Initiative
(Pooled-RotterdAm-Milano-Toulouse In
Collaboration). J Am Coll Cardiol. 2013;61(8):
830-836.
38. Meijboom WB, Mollet NR, Van Mieghem CAG,
et al. Pre-operative computed tomography
coronary angiography to detect significant
coronary artery disease in patients referred for
cardiac valve surgery. J Am Coll Cardiol.
2006;48(8):1658-1665.
39. Warkentin TE, Moore JC, Morgan DG.
Gastrointestinal angiodysplasia and aortic stenosis.
N Engl J Med. 2002;347(11):858-859.
40. Pellikka PA, Sarano ME, Nishimura RA, et al.
Outcome of 622 adults with asymptomatic,
hemodynamically significant aortic stenosis during
prolonged follow-up. Circulation.
2005;111(24):3290-3295.
JAMA October 9, 2013 Volume 310, Number 14
Downloaded From: http://jama.jamanetwork.com/ by a Beth Israel Deaconess Medical Center User on 09/24/2014
1497