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After revascularization, stress echocardiography can help identify high-risk asymptomatic patients, but it provides no better guidance for patient management than standard exercise testing and clinical profiling, according to data published online May 14, 2012, ahead of print in the Archives of Internal Medicine. Moreover, reintervention based on imaging-identified ischemia does not appear to improve outcomes.

Investigators led by Thomas H. Marwick, MD, PhD, MPH, of the Cleveland Clinic Heart and Vascular Institute (Cleveland, OH), assessed 2,105 asymptomatic patients who had undergone prior revascularization (PCI, n = 1,143; CABG, n = 962) and were referred for exercise echocardiography at their institution between January 2000 and November 2010.

Repeat Revascularization Uncommon

Overall, 17% of patients (n = 354) underwent repeat revascularization, including 13% (n = 262) who showed ischemia on the initial stress echocardiogram. However, 75% of those receiving repeat revascularization (n = 266) did not have ischemia on the initial echocardiogram, although it was detected in 24% of patients (n = 63) on subsequent testing performed after development of spontaneous symptoms.

According to the authors, the decision to proceed with repeat revascularization was based more on patients’ clinical status than solely on the result of exercise echocardiography. In fact, among ischemic patients, symptom status was the only variable associated with the decision for revascularization (P = 0.008).

Over an average follow-up of 5.7 years, 4.6% of patients died (n = 97). Mortality was about twice as high among those with ischemia on any exercise echocardiography compared with those without ischemia (8.0% vs. 4.1%; P = 0.03). Overall, however, most deaths occurred in nonischemic patients, and the annualized mortality rate was equivalent between those who did or did not undergo repeat revascularization (0.7% vs. 0.8%; P = 0.15). Of 21 deaths among ischemic patients, again, the annualized rates were similar between those who did and did not receive repeat revascularization (1.4% vs. 2.1%; P = 0.38).

Ischemia, Not Echo, Predicts Mortality

In multivariate analysis, ischemia was strongly associated with risk of cardiac mortality. Several other clinical predictors were also identified:

• Ischemia on exercise echocardiography (HR 2.10; P = 0.04)
• Prior CABG (HR 2.39; P < 0.001)
• Abnormal exercise echocardiogram without ischemia (HR 1.95; P = 0.03)
• Exercise capacity (HR 0.82; P = 0.003)
• Ejection fraction > 50% (HR 0.97; P = 0.02)
• Diabetes (HR 1.66; P = 0.03)

Importantly, in nested models, clinical and stress test findings were associated with both all-cause and cardiac mortality, but echocardiographic features were not.

In the overall population, repeat revascularization was not associated with improved survival (P = 0.67). The lack of association persisted even after taking into account interaction with an abnormal exercise echocardiogram. In addition, the degree of ischemia had no impact on the absence of benefit.

Whether stratifying patients by individual cardiac risk factors or a composite risk profile, the researchers were unable to identify subgroups of asymptomatic patients for whom exercise echocardiography and subsequent revascularization might be beneficial. In addition, the timing of exercise echocardiography after revascularization did not predict mortality in multivariate analysis (HR 0.89; 95% CI 0.56-1.40; P = 0.61).

The authors write that after revascularization, “screening tests are often considered in the hope of identifying and resolving [problems like restenosis or new lesions] electively and reducing the likelihood of acute presentations.” However, they add that it remains unknown whether the information provided by testing asymptomatic patients alters treatment, and, if so, whether such treatment changes alter outcomes.

“This is a critical issue because the detection of clinically silent coronary disease progression may expose the patient to the risks and expense of further revascularization without a survival benefit,” they write.

Little Benefit, Added Cost

In an accompanying editorial, Mark J. Eisenberg, MD, MPH, of McGill University (Montreal, Canada), says the study results “make a compelling argument that routine periodic stress testing in asymptomatic patients following coronary revascularization is of little clinical benefit.” Moreover, it is associated with high cost and resource utilization, and since most positive test results in this setting will be false-positive, it could lead to further testing and additional angiographic procedures.

Dr. Eisenberg suggests the need for a large trial randomizing asymptomatic patients to routine periodic stress testing or conservative management, and until “well-supported data” become available, “routine testing in asymptomatic patients is probably not worth the effort.”

New Era of Low Risk Key to Findings

George A. Beller, MD, of the University of Virginia Health System (Charlottesville, VA), told TCTMD in a telephone interview that the findings are not surprising given the low-risk nature of the study population, which was characterized by a near-normal ejection fraction and a reasonable exercise capacity. The prevalence of ischemia in this group is expected to be low, he said, and numerous studies have shown that such patients face a low risk of future events. Thus, stress imaging would be unlikely to provide incremental value over standard treadmill testing.

“The nature of revascularization has changed over the last 10 years or so compared to when the original data were published showing the value of exercise imaging in asymptomatic patients,” Dr. Beller observed. “That was before drug-eluting stents when there was a lot of restenosis and recurrent ischemia.” Also, today revascularization has become more complete, especially with use of fractional flow reserve to identify functional ischemia, he added. 

“Another factor that has changed is that 85% of these patients were on statins,” Dr. Beller noted. “When you’re on guidelines-based therapy, the chances of coronary disease progressing over 5 years after revascularization are much less.”

Still, the study’s conclusions apply only to low-risk asymptomatic patients, Dr. Beller cautioned, noting that a take-home message is to try to identify higher-risk subsets who may benefit. These might include patients whose risk factors are not well controlled, who have angina surrogates such as dyspnea, or diabetics who had significant silent ischemia before revascularization.

Exceptions to the Rule

In a telephone interview with TCTMD, Ajay J. Kirtane, MD, SM, of Columbia University Medical Center (New York, NY), noted that the study is observational and clearly not definitive. “But in the big picture, this article would support current guidelines—we probably shouldn’t be doing routine stress testing in all patients,” he said. “But the problem with generalizations like that is that there are situations in which it can be very useful.”

For example, after incomplete revascularization, a patient may report no symptoms, but the physician suspects that she is not being forthcoming. Another example is an AMI patient. “Say you revascularize the culprit lesion but leave behind residual disease. You would want to know, Should I revascularize the other lesions as well?” Dr. Kirtane said. “Post MI, that patient may be asymptomatic, and stress testing, particularly if it includes imaging, can be an important way to decide what to do.”

Study Details

The stress imaging was performed a mean of 4.1 ± 4.7 years after index revascularization. Testing was considered ‘late’ (> 2 years post-PCI and > 5 years post-CABG ) in 38% of PCI patients and 45% of CABG patients. Stress testing suggested the study group was relatively low risk. The mean exercise capacity was 8.7 METs (metabolic equivalents for task) and the mean resting ejection fraction was 53%. Ischemia was found in only 13% of patients.

2. Eisenberg MJ. Routine periodic stress testing in asymptomatic patients following coronary revascularization: Is it worth the effort? [invited commentary] Arch Intern Med. 2012;Epub ahead of print.

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