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N Engl J Med, Vol. 346, No. 9 ·
February 28, 2002 ·
www.nejm.org · 677 C L I N I C A L P R AC T I C E
Clinical Practice This
Journal feature begins with a case vignette highlighting a common clinical problem. Evidence supporting various strategies is then presented, followed by a review of formal guidelines, when they exist. The article ends with the author’s clinical recommendations. A ORTIC S TENOSIS
B LASE
A. C
ARABELLO
, M.D.
From the Department of Medicine, Baylor College of Medicine, and the Veterans Affairs Medical Center, Houston. Address reprint requests to Dr. Carabello at the Veterans Affairs Medical Center Medical Service (111), 2002 Holcombe Blvd., Houston, TX 77030, or at blaseanthony.carabello@ med.va.gov.
A 60-year-old man is evaluated for a heart mur- mur. He jogs 3 mi (5 km) per day and is asymp- tomatic. Physical examination reveals a delayed carotid upstroke, a 3/6 late-peaking systolic ejec- tion murmur that radiates to the neck, and a sin- gle S
. An echocardiogram shows normal systol- ic function and a heavily calcified aortic valve. The patient’s peak Doppler transvalvular gradient is 64 mm Hg, with a mean gradient of 50 mm Hg. His calculated valve area is 0.7 cm
2
. How should this patient be treated? THE CLINICAL PROBLEM
Aortic stenosis is the most common cardiac-valve lesion in the United States. Two factors account for its common occurrence: approximately 1 to 2 per- cent of the population is born with a bicuspid aortic valve, which is prone to stenosis; and aortic stenosis develops with age, and the population is aging. The clinician is usually first alerted to the presence of aortic stenosis by the finding of a systolic ejection murmur at the right upper sternal border that radiates to the neck. Clues that the disease is at least moderate in severity are peaking of the murmur late in systole, palpable delay of the carotid upstroke, and a soft sin- gle second heart sound, because the aortic component of S
disappears when the valve no longer opens or closes well. Although once thought of as a degenerative lesion, calcific aortic stenosis has many features in common with coronary disease.
1
Both conditions are more com- mon in men, older persons, and patients with hyper- cholesterolemia, and both derive in part from an ac- tive inflammatory process.
2
Aortic stenosis is distinguished from aortic sclero- sis by the degree of valve impairment. In aortic scle- rosis, the valve leaflets are abnormally thickened, but obstruction to outflow is minimal, whereas in aortic stenosis, the functional area of the valve has decreased enough to cause measurable obstruction of outflow. Little hemodynamic disturbance occurs as the valve area is reduced from the normal 3 to 4 cm
2
to 1.5 to 2 cm
2
. However, as shown in Table 1, an addition- al reduction in the valve area from half its normal size to one quarter of its normal size produces severe obstruction to flow and a progressive pressure over- load on the left ventricle. The concentric hypertrophy that develops in response to this overload is both adap- tive and maladaptive. Whereas the increased muscle mass allows the ventricle to generate the increased force necessary to propel blood past the obstruction, the hypertrophied myocardium has decreased coro- nary blood flow reserve
3 (even in the presence of nor- mal epicardial coronary arteries) and can also cause both diastolic and systolic left ventricular dysfunction, producing the symptoms of congestive heart failure.
4,5 The obvious question for the physician is when is the optimal time for clinical intervention? Although aor-
*Data were derived with the Gorlin formula: aortic-valve area = cardiac output÷(systolic ejection period¬heart rate) 44.3
mean gradient where the cardiac output was assumed to be 6 liters per min- ute, the systolic ejection period was assumed to be 0.33 sec- ond, and the heart rate was assumed to be 80 beats per minute.
R ELATION
OF
THE
A
ORTIC
-V ALVE
A
REA
TO
THE M
EAN
G RADIENT
.*
A ORTIC -V ALVE A REA M EAN G RADIENT
cm 2
mm Hg
4 1.7 3 2.9 2 6.6
1 26 0.9 32 0.8
41 0.7
53 0.6
73 0.5
105
, 678 ·
N Engl J Med, Vol. 346, No. 9 ·
February 28, 2002 ·
www.nejm.org Th e Ne w E n g l a nd Jo u r n a l o f Me d ic i ne
tic stenosis often coexists with other valvular diseases, this review focuses on isolated aortic stenosis. STRATEGIES AND EVIDENCE
There is no effective medical therapy for severe aortic stenosis; aortic stenosis is a mechanical obstruc- tion to blood flow that requires mechanical correction. In children with congenital aortic stenosis, the valve leaflets are merely fused, and balloon valvotomy may offer substantial benefit.
6 In adults with calcified valves, however, balloon valvotomy only temporarily relieves symptoms and does not prolong survival.
7
Thus, the intervention required in adults, other than standard prophylactic antibiotics against infective en- docarditis,
8 is the replacement of the valve. The risks of replacing that valve must be weighed against the risks of delaying the procedure. The procedure can usually be delayed until symptoms develop.
9,10 Stud-
ies of aortic stenosis uniformly demonstrate that once angina, syncope, dyspnea, or other symptoms of heart failure develop and are found to be due to aortic ste- nosis, the patient’s life span is drastically shortened un- less the valve is replaced (Fig. 1). Of the 35 percent of patients with aortic stenosis who present with an- gina, half will die within five years in the absence of aortic-valve replacement. Of the 15 percent of pa- tients who present with syncope, half will die within three years, and of the 50 percent of patients who present with dyspnea, half will die within two years, unless the aortic valve is replaced. In contrast, 10-year age-corrected rates of survival among patients who have undergone aortic-valve replacement approach the rate in the normal population.
11,12 The striking contrast between the excellent prog- nosis after aortic-valve replacement and the dismal prognosis in the absence of replacement in sympto- matic patients makes the presence or absence of symp- toms the crucial factor with respect to management. In general, the clinician can be confident that, in a giv- en patient, the symptoms are due to aortic stenosis if the mean aortic-valve gradient exceeds 50 mm Hg or if the aortic-valve area is no larger than 1 cm
2
. I will use these as criteria for severe disease, although there is no universally accepted definition that relies on valve area or gradient. AREAS OF UNCERTAINTY Management of Severe Asymptomatic Aortic Stenosis
There is overwhelming evidence that patients with severe aortic stenosis who become symptomatic re- quire prompt aortic-valve replacement. Conversely, asymptomatic patients, even those with severe disease, generally have an excellent prognosis without aortic- valve replacement. Unfortunately, approximately 1 to 2 percent of asymptomatic patients die suddenly or have a very rapid rate of progression to the sympto- matic state and then to sudden death.
9,10,13,14 Thus, the question arises whether patients with severe asymp- tomatic aortic stenosis should undergo aortic-valve re- placement to protect them from sudden death. Al- though some experts advocate this approach, this strategy exposes the entire group of asymptomatic pa- tients with severe aortic stenosis to the risk of peri- operative and valve-related complications and death. Even in the best of circumstances, the surgical mor- tality rate is approximately 1 percent and the risk of a valve-related complication (including thromboem- bolism; bleeding during therapy with anticoagulants; deterioration of the prosthetic valve, requiring reoper- ation; and infective endocarditis) is 1 percent per year.
15 Echocardiography and exercise testing may identify asymptomatic patients who are likely to benefit from surgery. Otto et al.
16
found that patients with asymp- tomatic aortic stenosis whose peak transaortic blood flow velocity exceeded 4 m per second (a peak gradi- ent of 64 mm Hg) had a risk of becoming symptomat- ic and requiring aortic-valve replacement of 70 percent within two years. None of the patients in this mod- erate-sized series died suddenly, and all underwent exercise testing. Although exercise testing is unwarranted and dan- gerous in patients with symptomatic aortic stenosis, it has proved safe in patients with moderate-to-severe asymptomatic aortic stenosis.
16,17
A preliminary report suggests that exercise testing may identify some pa- tients with latent symptoms or exercise-induced he- modynamic instability, facilitating timely aortic-valve replacement. In a study of 58 asymptomatic patients,
18
21 had symptoms for the first time during the exer- cise test. Most likely, these patients had failed to rec- ognize the symptoms previously or had not engaged in activities that would have precipitated symptoms. Although patients with asymptomatic aortic stenosis can exercise safely under a physician’s scrutiny, it seems most unwise to permit patients with moderate-to- severe aortic stenosis to engage in vigorous, unmon- itored exercise in view of the limitations imposed by left ventricular hypertrophy on coronary blood flow. Treatment of the Patient with a Low Gradient and Reduced Ejection Fraction
In patients with left ventricular dysfunction who have a substantial transvalvular gradient (a mean gra- dient of more than 40 mm Hg), the outcome of sur- gery is excellent despite the presence of a reduced ejec- tion fraction preoperatively.
19
In these patients, the excessive afterload generated by the obstructing valve is a prime contributor to the left ventricular dysfunc- tion. Once the obstruction is removed and the after- load is reduced, left ventricular function returns to or approaches normal. Patients with a reduced ejection fraction and a small
C L I N I C A L P R AC T I C E
N Engl J Med, Vol. 346, No. 9 ·
February 28, 2002 ·
www.nejm.org · 679
transvalvular gradient (less than 30 mm Hg) 19,20
have
a high operative risk, and only half such patients are alive three to four years after surgery.
21
The poor out- come in these patients is related to the presence of both severely depressed myocardial contractility and the excessive afterload.
19
Although the overall prognosis for this group of pa- tients is poor, some patients in this category, pre- sumably those with severe valve obstruction, benefit from surgery.
21,22
In other patients, the calculated valve area may be severely reduced because cardiomyopathy inhibits the left ventricle from completely opening a mildly but not a severely stenotic valve. The presence of low output may lead clinicians to the false conclu- sion that the valve is severely stenotic (aortic pseudo- stenosis).
23-25
The best method for distinguishing these two conditions is to increase cardiac output during Doppler echocardiography or cardiac catheterization Figure 1.
Survival among Patients with Severe Symptomatic Aortic Stenosis Who Underwent Valve Replacement and Similar Patients Who Declined to Undergo Surgery. The overall and individual P values are shown, as is the overall chi-square value. Reprinted from Schwarz et al.
11 with the permission of the publisher. 0 100
0 5 20 40 60 80 1 2 3 4 Year
Valve replacement Chi-square=23.5 P<0.001 No surgery P<0.001 P<0.05
Survival (%) N O. AT R ISK
Valve replacement No surgery 125 0
87 0 8 51 0 2 35 0 1 9 0 0 0 680 ·
N Engl J Med, Vol. 346, No. 9 ·
February 28, 2002 ·
www.nejm.org Th e Ne w E n g l a nd Jo u r n a l o f Me d ic i ne
and to use the new data to recalculate the valve area. In the case of pseudostenosis, increased output causes a large increase in the calculated valve area, often to more than 1 cm
2 . In this group of patients, valve re- placement is unlikely to be beneficial. Conversely, pa- tients in whom increased cardiac output produces a substantial increase in gradient have a true outflow obstruction and may benefit from surgery. Patients with a low gradient who have no response to ino- tropic stimulation have a poor outcome, presumably because the myocardial damage is so far advanced.
26 Safety of Cardiac Surgery in Patients with Mild-to-Moderate Aortic Stenosis
Controversy also exists regarding the optimal ap- proach to patients with mild-to-moderate aortic steno- sis (as indicated by a transvalvular gradient in the range of 10 to 30 mm Hg and a valve area of more than 1 cm
2
) who require cardiac surgery for some other cause, usually coronary revascularization. Concomitant aortic-valve replacement increases the risk of both per- ioperative death and complications related to the pros- thetic valve. However, if the native valve is left in place, aortic stenosis may progress so rapidly that another cardiac surgery is required despite the fact that the bypass grafts are functioning normally.
27
Unfortunate- ly, there is wide individual variability in the rate of dis- ease progression,
27-29 virtually precluding prognosti- cation of the course of a given patient. Concomitant aortic-valve replacement is considered unwise if it is likely to increase the gradient even further.
On the basis of a small number of adverse events, one study indicated that noncardiac surgery posed an increased risk among patients with aortic stenosis.
30
However, O’Keefe et al. examined the course of 48 patients with severe aortic stenosis who underwent noncardiac surgery
31 and found that there were no complications in the 25 patients who had local anes- thesia and only one complication in the 23 patients who received general anesthesia. Thus, although intra- operative hemodynamics must be closely monitored during noncardiac surgery in patients with asympto- matic aortic stenosis, there is no apparent need for concomitant aortic-valve intervention.
As noted above, the lesion of aortic stenosis shares many features with coronary disease. Although recent data suggest that hydroxymethylglutaryl coenzyme A reductase inhibitors (referred to as “statins”) can retard the progression of aortic stenosis,
32
in my opinion it is a bit too early to begin prescribing statins for this purpose.
Guidelines for the use of valve replacement in pa- tients with aortic stenosis are provided in Table 2. In 1998 the American Heart Association and American College of Cardiology issued guidelines for the treat- ment of valvular heart disease (available at http:// www.americanheart.org).
8 These guidelines recom- mend the use of standard antibiotic prophylaxis against infective endocarditis. Doppler echocardiography is recommended for the initial diagnosis and assessment of the severity of aortic stenosis and the function and hemodynamics of the left ventricle, as well as for the reevaluation of patients whose symptoms and signs are changing and of patients known to have severe asymptomatic aortic stenosis. CONCLUSIONS AND RECOMMENDATIONS
Doppler echocardiography is indicated for the ini- tial evaluation in all patients suspected of having aortic stenosis, as well as in patients with established disease if symptoms develop or physical signs change. The de- velopment of angina, syncope, or dyspnea in a patient with severe aortic stenosis constitutes a grave medical condition, requiring prompt aortic-valve replacement. For patients with severe asymptomatic disease, such as the patient described in the clinical vignette, the presence of an aortic-jet velocity of at least 4 m per second on Doppler echocardiography indicates the need for close scrutiny. I routinely recommend ex- ercise testing in this group (but never in symptomat- ic patients), since it may help identify which of these patients are at high enough risk to warrant undergo- ing surgery (Fig. 2). The postoperative prognosis of patients with a re- duced ejection fraction is good if the mean transval- vular pressure gradient exceeds 40 mm Hg. Thus, a low ejection fraction alone should never be an abso-
*Aortic-valve replacement is not indicated to prevent sudden death in asymptomatic patients who have none of the findings listed. T ABLE 2.
R ECOMMENDATIONS
FOR
THE
U
SE
OF
A
ORTIC -V
ALVE
R
EPLACEMENT
IN
P ATIENTS
WITH
A ORTIC
S
TENOSIS
. Aortic-valve replacement indicated
Patients with severe aortic stenosis and any of its classic symptoms (angina, syncope, or dyspnea) Patients with severe aortic stenosis who are undergoing coronary-artery by- pass surgery Patients with severe aortic stenosis who are undergoing surgery on the aor- ta or other heart valves
Patients with only moderate aortic stenosis who require coronary-artery by- pass surgery or surgery on the aorta or other heart valves Asymptomatic patients with severe aortic stenosis and at least one of the following: an ejection fraction of no more than 0.50, hemodynamic in- stability during exercise (e.g., hypotension), or ventricular tachycardia* C L I N I C A L P R AC T I C E
N Engl J Med, Vol. 346, No. 9 ·
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lute contraindication to surgery. However, the prog- nosis of patients with a low gradient and a low ejec- tion fraction is worse. For such patients I recommend hemodynamic manipulation in the catheterization or echocardiographic laboratory to help determine which patients are more likely to benefit from surgery. Preliminary evidence indicates that patients who have moderate aortic stenosis (as indicated by a gra- dient of more than 20 mm Hg and a valve area of less than 1.2 cm
2 ) but who require heart surgery for oth- er diseases should probably undergo concomitant aor- tic-valve replacement. Further study of this approach is required.
Otto CM, Kuusisto J, Reichenbach DD, Gown AM, O’Brien KD. Char- acterization of the early lesion of “degenerative” valvular aortic stenosis: histological and immunohistochemical studies. Circulation 1994;90:844- 53.
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Marcus ML, Doty DB, Hiratzka LF, et al. Decreased coronary reserve: a mechanism for angina pectoris in patients with aortic stenosis and normal coronary arteries. N Engl J Med 1982;307:1362-7. 4.
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McCrindle BW. Independent predictors of immediate results of percu- Figure 2.
Algorithm for the Management of Aortic Stenosis. Aortic stenosis without symptoms present on physical examination Severe
aortic stenosis and symptoms present on physical examination Perform Doppler echocardiography If echocardiography shows mild-to-moderate aortic stenosis, monitor patient for the development of symptoms If echocardiography shows severe aortic stenosis, perform exercise testing If results are normal,
monitor patient
closely If symptoms develop, repeat
echocardi- ography
If aortic stenosis becomes severe,
perform coronary arteriography and aortic- valve replacement If patient remains
asymptomatic but findings on examination change, repeat echocardi- ography
If aortic stenosis remains mild to moderate, continue follow-up If results are abnormal, perform coronary arteriography and aortic-valve replacement Mild-to-moderate aortic stenosis and symptoms present on physical examination Search for other causes of symptoms Perform
coronary arteriography and aortic-valve replacement 682 ·
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dures in patients with aortic stenosis. Mayo Clin Proc 1989;64:400-5. 32. Novaro GM, Tiong IY, Pearce GL, Lauer MS, Sprecher DL, Griffin BP. Effect of hydroxymethylglutaryl coenzyme A reductase inhibitors on the progression of calcific aortic stenosis. Circulation 2001;104:2205-9. Copyright © 2002 Massachusetts Medical Society. IMAGES IN CLINICAL MEDICINE The Journal welcomes consideration of new submissions for Images in Clinical Medicine. Instructions for authors and procedures for submissions can be found on the Journal’s Web site at http://www.nejm.org. At the discretion of the editor, images that are accepted for publication may ap- pear in the print version of the Journal, the electronic version, or both. Yüklə 84,85 Kb. Dostları ilə paylaş:
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