Timing of Aortic Valve Replacement in Aortic Stenosis
Abstract & Commentary
Synopsis: Individuals with aortic stenosis without valve calcification are a low-risk subgroup and may remain event-free for many years.
Source: Rosenhek R, et al. N Engl J Med 2000;343:611-617.
In 1997 otto and associates reported a prospective study of asymptomatic individuals with valvular aortic stenosis.1 They concluded that one of the most important factors predicting the need for ultimate aortic valve replacement (AVR) was a peak aortic valve velocity of more than 4 m/sec by Doppler echo. In addition, the rate of yearly progression of aortic valve narrowing was an important factor. This new study adds additional information to the sometimes difficult problem of deciding when to intervene in a patient with severe aortic stenosis who has no symptoms. This is a prospective analysis from Vienna that followed 128 asymptomatic patients with severe aortic stenosis. All had a mean aortic velocity greater than 4 m/sec; the mean baseline velocity was 5.0 ± 0.6 m/sec. Left ventricular function was preserved. Conventional echocardiographic clinical parameters were carefully noted; subjects were followed from 1994 to 1998. Two patients were lost to follow-up and 22 of the initial 128 patients underwent elective AVR within three months of enrollment in the study. The primary end point was cardiovascular death or need for AVR in the remaining106. Follow-up was 22 ± 18 months.
A total of eight deaths and 59 AVRs occurred because of development of symptoms. Kaplan-Meier curves indicated that event-free survival was poor, although the death rate was low. Of the entire group, 33% had an AVR by year one, 44% by year two, and 67% by four years. There was only one sudden death not preceeded by symptoms. Other deaths were due to aortic valve complications in symptomatic patients. Of the 59 patients who underwent AVR, the follow-up period was 28 ± 15 months. Overall acturial probability of survival was 93% at one year and 87% at four years.
Predictors of outcome included age older than 50, coronary artery disease, and diabetes. However, only older age affected long-term results (event-free survival for patients younger than 50 was 85% at one year and 60% at four years; for patients older than 50, (59% at 1 year and 21% at 4 years). A major predictor of outcome was the extent of aortic valve calcification. Individuals with moderate to severe calcification did poorly, and all deaths occurred in this group. Patients with no or mild calcification did well; 92% event-free at one year and 75% at four years, compared to 60% and 20% respectively, for those with significant calcification. No events occurred in 11 patients without demonstrable calcification on echocardiography with a mean follow-up of over three years. Aortic valve velocity was only slightly higher in those who had cardiac events; however, the rate of progression of velocity increase was greater in patients who had cardiac events (0.45 ± 0.38 vs 0.14 ± 0.18 m/sec/y [P < 0.001]). Among patients with a heavily calcified valve, the outcome was poor with an event outcome comparable to those older than 50 years. Severe aortic valve calcification and a rapid increase in aortic jet velocity identified a high-risk group. Those with an increase of 0.3 m/sec within one year and significant calcification had an 80% likelihood of need for surgery or death within two years.
Rosenhek and colleagues comment that their data and other studies show that sudden death may occur in the absence of overt symptoms in patients with severe aortic stenosis but is uncommon and is estimated to be less than 1% per year. Conversely, patients who develop symptoms required surgery within a very short time period. Factors that predict outcome in previous studies include aortic jet velocity, ejection fraction, and functional status, but not all trials reached the same conclusion. This study emphasizes the importance of extensive valve calcification. Rosenhek et al conclude that an annual echocardiogram is important in patients with asymptomatic aortic stenosis, and it is "relatively safe to delay surgery until symptoms develop." Surgical outcomes were less optimal in individuals who became symptomatic. They conclude that individuals with aortic stenosis without valve calcification are a low-risk subgroup and may remain event-free for many years. The majority of rapid progressors will require an AVR or will die within several years, and such individuals should be carefully monitored.
Comment by Jonathan Abrams, MD
This study adds to the important database of Otto et al. which did not report calcification as an independent risk factor, but this was an important observation in the Austrian study. Older age is clearly a risk factor, although it may be confounded by the ubiquity of calcification in individuals older than 50-60 years. In an accompanying editorial, Otto stresses that calcific aortic valve disease is not merely a denegerative condition of aging but "represents the end stage of active disease process." She emphasizes the depostion of lipoproteins, macrophages, and T-lymphocytes in the aortic valve, with osteopontein production in regions of macrophage concentration. She estimates that 25% of adults older than age 65 have aortic sclerosis, a small number of whom will progress to aortic stenosis. Clinically significant aortic stenosis is present in 1-2% of subjects older than 65. Any individual with a prominent systolic ejection murmur in this age group should undergo echocardiography, as it is often difficult to differentiate aortic sclerosis with aortic stenosis in the elderly. Otto also focuses on the presence or the absence of symptoms as being a primary determinate of outcome. "In contrast, adults with asymptomatic aortic stenosis have an excellent clinical prognosis." Velocity progression in the Austrian study 0.3 m/sec per year and/or a decrease in aortic valve area of 0.1cm2 per year is to be expected, with wide individual variation.
In conclusion, patients with moderately severe to severe aortic stenosis without symptoms can be safely followed with serial echocardiography, but when severe calcification is present, or there is left ventricular dysfunction, consideration of preemptive surgery should be given. This study confirms that a rapid increase in the aortic valve velocity on serial echo should be a signal for surgery. Sudden death is rare in these individuals but may occur. For the clinician, a combination of a careful examination, history taking, and the use of high quality 2-D echocardiography should make the decision of when to intervene relatively straightforward, based on the data accumulated in these two important recent studies.
Reference
- Otto CM, et al. Circulation 1997;95:2262-2270.
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