Role of stress testing after coronary artery revascularization

INTRODUCTION — Noninvasive cardiac stress testing is an important tool in the evaluation and assessment of patients with symptoms suggestive of coronary heart disease (CHD) prior to coronary revascularization. Noninvasive cardiac stress testing also plays a valuable role following cardiac procedures such as percutaneous coronary intervention (PCI) and coronary artery bypass graft surgery (CABG) in assessing:

●The potential ischemic etiology of recurrent or new symptoms suggestive of myocardial ischemia

●The presence and significance of incomplete revascularization

●The occurrence of restenosis

●The development of new stenoses in bypass grafts, and the progression of native CHD following either procedure

This section will discuss stress testing and particularly stress imaging with either radionuclide myocardial perfusion imaging (rMPI) or transthoracic echocardiography. The use of imaging prior to revascularization to detect hibernating myocardium (ie, dysfunctional but viable myocardium) and general considerations on the role of stress testing for the diagnosis and prognosis CHD are discussed separately. (See "Assessment of myocardial viability by nuclear imaging in coronary heart disease" and "Dobutamine stress echocardiography in the evaluation of hibernating myocardium" and "Selecting the optimal cardiac stress test" and "Prognostic features of stress testing in patients with known or suspected coronary disease".)

STRESS IMAGING AFTER CORONARY REVASCULARIZATION — In most patients, cardiac stress testing following revascularization should be driven by the presence of symptoms rather than empirically performed for screening. The goal of cardiac stress testing after revascularization is not only to evaluate for restenosis but also to determine the functional status, hemodynamic response to exercise, and symptoms of the patient. There are few data (particularly randomized controlled trials) regarding the routine evaluation of asymptomatic patients post-revascularization, and cardiac stress testing for this reason is generally not recommended or necessary, with few exceptions such as patients who had percutaneous coronary intervention (PCI) or coronary artery bypass graft surgery (CABG) for silent ischemia (ie, asymptomatic or atypical symptoms prior to revascularization) [1].

Stress testing following PCI can identify myocardial ischemia resulting from in-stent restenosis, the progression of coronary lesions in arteries that were not revascularized, or the development of de novo lesions. Stress testing after CABG can identify ischemia due to graft disease, downstream lesions, anastomotic lesions, progression of atherosclerosis in native non-grafted vessels, and incomplete revascularization. Ischemia after PCI or CABG can occur with patent stents and patent grafts because of jailed branches after PCI (eg, septal perforators or diagonal branches after stenting the left anterior descending artery [LAD]) or jeopardized branches after CABG (eg, septal perforators or diagonal branches arising from non-revascularized proximal LAD between sequential LAD stenoses even though the graft to distal LAD is patent). This is a big difference between post PCI/CABG patients and those with native disease alone.

With radionuclide myocardial perfusion imaging (rMPI) and echocardiography, a septal wall motion abnormality is common after CABG and not suggestive of myocardial necrosis, although myocardial scarring may be detected after seemingly uncomplicated procedures.

This section will review the role of stress testing in the detection of ischemia related to new or recurrent obstructive coronary heart disease (CHD) following revascularization with either PCI or CABG. A second issue, the use of stress rMPI or stress echocardiography prior to revascularization to detect hibernating myocardium (ie, dysfunctional but viable myocardium), is discussed separately. (See "Assessment of myocardial viability by nuclear imaging in coronary heart disease" and "Dobutamine stress echocardiography in the evaluation of hibernating myocardium".)

Choice of stress test — Stress rMPI and stress echocardiography are both useful imaging techniques in the evaluation of patients with CHD. The choice of test will vary depending upon local expertise and local availability as well as the clinical scenario. (See "Selecting the optimal cardiac stress test".)

When symptoms suggestive of obstructive CHD indicate the need for stress testing in patients with a history of revascularization, exercise electrocardiography (ECG) alone is rarely the preferred test, as the site and extent of any ischemia cannot be assessed. The need to identify the ischemia location with stress imaging in patients who have undergone prior revascularization is generally far more valuable than in a general population undergoing stress testing as an initial diagnostic tool, for whom ECG alone is often satisfactory. Therefore, when stress testing is performed for diagnosis of ischemia among patients who have undergone either PCI or CABG, we agree with recommendations from published society guidelines regarding the choice of stress test and imaging [1,2]:

●Exercise/physiologic stress with imaging using rMPI or echocardiography should be performed in patients who are able to exercise.

●Vasodilator (regadenoson, adenosine, or dipyridamole) rMPI or dobutamine echocardiography should be performed in patients who are not able to exercise.

There are two main reasons for recommending cardiac stress testing with imaging rather than exercise ECG testing alone after coronary revascularization:

●The sensitivity for detecting ischemia is significantly lower with exercise ECG testing alone compared with stress imaging [3]. As an example, the sensitivity of exercise ECG stress testing for the identification of ischemia related to graft stenosis or progression of underlying CHD was only 45 percent (compared with a sensitivity in the 80 to 85 percent range for both stress rMPI and stress echocardiography) [3].

●The documentation of both the site (vascular territory) and extent of ischemia is possible when stress testing is performed with imaging.

Both rMPI and echocardiography are adequate as the source of imaging when performing a stress test in patients who have undergone revascularization. A 2003 meta-analysis of nine studies evaluating stress rMPI and stress echocardiography for the detection of restenosis following PCI reported similar sensitivity and specificity for the two techniques (sensitivity and specificity 82 and 86 percent for stress echocardiography, 83 and 79 percent for stress rMPI) [4]. It is important to note that the reference gold standard for CHD diagnosis in these studies was coronary angiography based on percent diameter stenosis, which is flawed, and these studies did not address the myriad causes of ischemia unrelated to stent or graft patency. The published society guidelines express no preference between the two imaging techniques [1].

Role of exercise ECG testing without imaging — While exercise ECG testing without imaging is rarely indicated for the evaluation of symptomatic patients with prior revascularization, this test is sometimes performed as a means to guide the prescription of exercise for cardiac rehabilitation programs following either PCI or CABG or for assessing the hemodynamic response to exercise. The use of exercise ECG testing in this setting is discussed separately. (See "Cardiac rehabilitation programs", section on 'Intensity'.)

Prognostic value of post revascularization stress testing — Both radionuclide rMPI and stress echocardiography have robust data supporting their role as a prognostic test following revascularization. Both imaging techniques have a high negative predictive value with a normal stress imaging result.

●In a meta-analysis of 21 studies assessing the prognostic value of exercise stress testing with imaging (17 rMPI studies with 8008 patients and four echocardiography studies with 3021 patients) in patients both with and without known CHD, the negative predictive value for the combination of myocardial infarction (MI) and cardiac death was 98.8 percent over 36 months of follow-up for rMPI and 98.4 percent over 33 months for echocardiography [5].

●Longer-term outcome following normal rMPI in patients with known CHD has also been shown to be excellent. In a cohort of 266 patients with known CHD (93 percent with prior revascularization, including 34 percent CABG and 59 percent PCI) who were following for a median of 12 years, annualized cardiac mortality rate was 0.9 percent, with an annualized rate for cardiac death and nonfatal infarction of 1.2 percent [6].

Test performance among reported studies is variable, related in part to differences in populations evaluated as well as the criteria for restenosis. Some of the factors influencing the correlation between stress testing and angiography include incomplete revascularization and the failure of angiographically-moderate single-vessel stenosis to lead to significant ischemia.

Evaluation of symptomatic patients

Patients with symptoms hours to days post-revascularization — Ischemic chest pain within 48 hours after PCI (with or without stenting) usually results from procedural events such as abrupt vessel closure (largely eliminated by stenting), transient coronary spasm, non-occlusive or occlusive thrombus, side branch occlusion, or distal embolization. Stress testing is not warranted in such patients, as patients with chest pain and ECG changes with a suspicion for an acute or subacute complication post-PCI generally require aggressive medical management and often repeat coronary angiography. (See "Periprocedural complications of percutaneous coronary intervention", section on 'Myocardial ischemia'.)

Ischemic chest pain in the hours to days following CABG usually results from early thrombotic occlusion of a saphenous vein bypass graft, often from a technical problem at the site of anastomosis. If symptoms are atypical, stress testing with imaging may be helpful in such patients to assess for size and distribution of any myocardial ischemia. However, since therapy for early saphenous vein bypass graft occlusion most commonly involves PCI, coronary angiography is often the preferred initial diagnostic test. (See "Early cardiac complications of coronary artery bypass graft surgery", section on 'Early graft occlusion'.)

Patients with symptoms months to years post-revascularization — Recurrent symptoms developing months to years following PCI or CABG generally represent development of new obstructive CHD or progression of previously non-critical CHD, although in-stent restenosis, stent thrombosis, bypass graft stenosis or occlusion, or other manifestations of CHD may also be late occurrences. In such patients, stress testing with imaging is very useful for the evaluation of symptoms and the determination of the distribution, extent, and severity of any myocardial ischemia. (See 'Stress imaging after coronary revascularization' above.)

Symptomatic patients following complete revascularization — In patients with recurrent anginal symptoms following what was thought to be complete revascularization (ie, no residual diameter stenosis >50 percent), stress testing with imaging is helpful for determining the distribution and extent of ischemia (if any), restenosis following PCI, graft failure following CABG, or the de novo development of a new obstructive CHD lesion. Additionally, imaging allows the clinician to identify the most likely anatomically associated coronary artery or bypass graft.

●In a single-center study of 346 patients who underwent stress rMPI (70 percent exercise, 30 percent dipyridamole) between 12 and 18 months post-PCI (94 percent with one or more stents, 79 percent deemed completely revascularized) and were followed for an average of 31 months, only 2 percent of patients without ischemia on rMPI had a hard event (cardiac death or myocardial infarction), compared with 12 percent of patients with ischemia on rMPI [7].

●Stress rMPI can accurately detect myocardial ischemia related to bypass graft stenosis, even in patients with atypical symptoms, and can aid in localizing the stenosis, particularly if gated single photon emission computed tomography (SPECT) imaging is performed. In one study of 50 patients with chest pain (atypical in 40 percent) an average of 51 months following CABG who all underwent both stress testing with rMPI and coronary angiography, the sensitivity and specificity of rMPI for detecting ischemia related to a 50 percent or greater stenosis were 80 and 87 percent, respectively [8].

●The diagnostic accuracy of stress echocardiography has also been evaluated in a number of studies [3,9,10]. In one meta-analysis, the sensitivity and specificity of stress echocardiography for the detection of graft stenosis or progression of native CHD after CABG were 86 and 90 percent, respectively [3]. There was a trend toward greater sensitivity with stress echocardiography compared with stress rMPI (86 versus 68 percent), while specificity was similar (84 versus 90 percent).

Symptomatic patients following incomplete revascularization — In patients with recurrent anginal symptoms following revascularization that was deemed incomplete (ie, following PCI of the most critical stenosis with residual stenoses in other territories), cardiac stress testing with imaging is helpful for determining the distribution and extent of ischemia (if any) related to residual stenoses and the most likely anatomically-associated coronary artery.

In a prospective single-center cohort of 322 consecutive patients who underwent exercise rMPI four to six months after incomplete revascularization and were followed for a median of 33 months, the yearly rate of cardiac events ranged from 1.5 to 5.1 to 8.5 percent in patients with normal, mildly abnormal, and severely abnormal findings on exercise rMPI [11]. In this setting, rMPI added incremental prognostic value to the clinical and angiographic findings and to the Duke treadmill score (DTS), particularly in patients with an intermediate or high score. (See "Prognostic features of stress testing in patients with known or suspected coronary disease", section on 'Duke treadmill score'.)

Asymptomatic patients — As a result of the dramatic decline in restenosis following revascularization with PCI in the era of drug-eluting stents and aggressive medical therapy, routine testing of asymptomatic patients post-PCI is no longer recommended. Similarly, given the durability of coronary artery bypass grafting in the majority of patients, routine testing of asymptomatic patients post-CABG is also not recommended. However, routine stress testing may be of value for risk stratification in asymptomatic patients when performed more than two years after PCI or more than five years after CABG. This approach is based upon the premise that a positive test identifies asymptomatic patients who have a worse prognosis and might benefit from intervention [12]. Regardless of imaging strategy, all patients should be treated with aggressive risk factor reduction (eg, aggressive antihypertensive and lipid-lowering therapy, smoking cessation, and lifelong antiplatelet therapy), which should slow the rate of progression and may even promote regression of native vessel disease. (See "Prevention of cardiovascular disease events in those with established disease (secondary prevention) or at very high risk".)

Evaluation of asymptomatic patients following PCI has evolved considerably from the era of balloon angioplasty alone, in which restenosis was common and occurred in patients with no symptoms. In the era of drug-eluting stents, the incidence of restenosis and thrombosis following PCI is very low, especially in asymptomatic patients. As such, routine stress testing of asymptomatic patients following revascularization for purposes of diagnosis is generally not necessary but continues to be performed within two years after revascularization by many clinicians [13-15].

While not routinely performed for diagnostic purposes in asymptomatic patients, stress rMPI or stress echocardiography can be important prognostically in asymptomatic patients, particularly those who were not completely revascularized [16-19]. There is no evidence to suggest, however, that those asymptomatic patients with ischemia would benefit from repeat revascularization procedures.

●In a meta-analysis of 29 studies (involving 12,874 patients, including 68 percent without symptoms) of stress imaging tests after revascularization, persons with an abnormal stress test had significantly more hard cardiac events (cardiac death or MI; hazard ratio 1.2, 95% CI 1.1-1.3) [19]. In another nonrandomized study, approximately 20 percent of asymptomatic patients were found to have inducible ischemia during stress echocardiography less than one year following PCI; patients with ischemia were more likely to die in the following five years [18].

●Among a cohort of 869 asymptomatic patients who underwent exercise stress echocardiography more than two years after PCI or more than five years after CABG (mean follow-up of an additional 5.7 years), those with inducible ischemia had significantly higher mortality [17]. Interestingly, repeat revascularization in this cohort did not result in a more favorable outcome. Similar prognostic findings with stress rMPI and stress echocardiography following CABG have been reported in numerous other cohorts, both early (less than five years) [20,21] and late (greater than five years) [22-26] post-CABG (figure 1).

Our approach to stress testing in patients post-revascularization — Although stress testing in patients with symptoms suggestive of CHD weeks to years following PCI is appropriate, multiple major society guidelines argue against routine stress testing of asymptomatic patients after successful PCI and CABG with complete revascularization [1,27,28]. Among patients referred for stress testing who can exercise, either exercise rMPI or exercise echocardiography is recommended. Among patients who cannot exercise, pharmacologic stress with imaging should be used. Exercise electrocardiogram (ECG) testing alone is not recommended because of the decrease in sensitivity and its inability to localize the site of disease [4].

We recommend the following approach to stress testing in patients following PCI:

●Choice of stress test and imaging modality:

•For patients who require stress testing post-PCI, the choice of imaging modality (ie, stress rMPI or stress echocardiography) is based upon local availability, expertise, and patient factors (eg, age/radiation exposure, acoustic windows). In general, we favor stress echocardiography for those patients with underlying normal resting left ventricular systolic function and stress rMPI for those with underlying regional dysfunction or vasodilator rMPI for those with resting left bundle branch block.

•Among patients who can attain an adequate level of exercise (defined as ≥85 percent of their predicted maximal heart rate), symptom-limited treadmill or bicycle exercise is the preferred form of stress because it provides the most information concerning patient symptoms, exercise capacity, cardiovascular function, and the hemodynamic response during usual forms of activity.

●Which patients to test:

•For patients with angina symptoms in the immediate post-PCI period (hours to days), we generally perform coronary angiography to assess for acute or subacute stent thrombosis.

•For patients with angina symptoms in the immediate post-CABG period (up to 30 days), we generally perform coronary angiography to assess for acute or subacute bypass graft thrombosis.

•For patients with late angina symptoms in the post-revascularization period (weeks to years), we perform stress imaging to assess whether these symptoms represent ischemia, to identify (when present) the ischemic territory, and to determine the exercise intensity (heart rate, blood pressure) precipitating ischemia to guide medical therapy.

•For asymptomatic patients following PCI or CABG (any time point) who are deemed fully revascularized, we do not perform routine stress testing unless they had no or atypical angina symptoms prior to revascularization. If no or atypical angina symptoms preceded PCI or CABG, we perform routine testing two to three years after PCI and five years after CABG, respectively.

•For asymptomatic patients following PCI or CABG (greater than two years post-PCI or greater than five years post-CABG) who are deemed incompletely revascularized, we consider stress rMPI or stress echocardiography if there is a concern for disease progression or in select high-risk patients (ie, patients with diabetes or those with silent ischemia).

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Heart failure in adults" and "Society guideline links: Chronic coronary syndrome" and "Society guideline links: Percutaneous coronary intervention" and "Society guideline links: Coronary artery bypass graft surgery" and "Society guideline links: Multimodality cardiovascular imaging appropriate use criteria" and "Society guideline links: Stress testing and cardiopulmonary exercise testing".)

SUMMARY AND RECOMMENDATIONS

●Noninvasive cardiac stress testing plays a valuable role following cardiac procedures such as percutaneous coronary intervention (PCI) and coronary artery bypass graft surgery (CABG) to assess the potential ischemic etiology of chest pain due to the presence and significance of incomplete revascularization, the occurrence of restenosis following PCI, the development of thrombosis or stenosis in bypass grafts, and the progression of native coronary heart disease (CHD). (See 'Introduction' above.)

●In nearly all patients, cardiac stress testing following revascularization should be driven by the presence of symptoms rather than routinely performed. The goal of cardiac stress testing after revascularization is not only to evaluate for restenosis but also to determine the functional status and patient symptoms. Routine stress testing of asymptomatic patients post-PCI or post-CABG is rarely recommended. (See 'Stress imaging after coronary revascularization' above and 'Asymptomatic patients' above.)

●Radionuclide myocardial perfusion imaging (rMPI) and echocardiography are both useful imaging techniques for stress testing in the evaluation of patients with CHD. The choice of imaging test will vary depending upon local expertise, local availability, and patient-specific factors (age/radiation exposure, acoustic windows). Exercise electrocardiogram (ECG) alone is rarely the preferred test, as the site and extent of any ischemia cannot be assessed. For patients with resting left bundle branch block, vasodilator rMPI is suggested. (See 'Choice of stress test' above.)

●Our approach to choosing which patients to test along with the most appropriate stress test modality and imaging modality is summarized within the topic. (See 'Our approach to stress testing in patients post-revascularization' above.)

ACKNOWLEDGMENT — The authors and UpToDate thank Dr. Georgios Papaioannou, who contributed to earlier versions of this topic review.