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New insights into diagnostic testing guidelines in women
by Thomas S. Metkus Jr., MD Fellow; Roger S. Blumenthal, MD; and Parag H. Joshi, MD
In response to the documented gap in appropriate diagnosis and treatment of ischemic heart disease between women and men, Jennifer H. Mieres, MD, FACC, FASNC, FAHA, and colleagues authored an update to the 2005 Guidelines on the Role of Noninvastive Testing in the Clinical Evaluation of Women with Suspected Ischemic Heart Disease. The consensus panel’s stated goal is to elucidate the role of diagnostic testing to stratify symptomatic women into those with no CAD, those with nonobstructive CAD and those with obstructive CAD, and prescribe appropriate evidence-based therapies thereafter.
It is hoped that this strategy will help shrink the outcomes gap between women and men with CAD. The authors take on the large task of assimilating volumes of data from multiple available diagnostic stress and imaging tests to evaluate symptomatic women.
Thomas S. Metkus, Jr.
Important highlights
The guideline update first highlights that a population of women with stable ischemic symptoms have a higher percentage of nonobstructive CAD at angiography, yet have an elevated hazard of future cardiac events compared with the general population. This significant observation highlights an important paradigm change in consideration of myocardial ischemia, which traditionally has been felt to be due to obstruction of flow from high-grade coronary lesions; however, it can also be due to vascular dysfunction in the setting of nonobstructive epicardial CAD leading to demonstrable regional myocardial hypoperfusion.
This finding indicates that women with a positive stress test, yet no obstructive coronary stenoses at angiography, can still have an abnormal test that connotes elevated future cardiac risk. This consideration essentially eliminates the concept of a “false positive” MPI stress test as long as there is any atherosclerosis.
In total, these observations by the panel recognize the importance of myocardial ischemia and the presence of any atherosclerosis by angiography, either invasive or by CT, as increased risk, even in the absence of obstructive CAD.
Pre-test probability, risk stratification
Roger S. Blumenthal
In choosing candidate symptomatic women for noninvasive testing, it is important to define the pre-test probability of disease. The authors point out that algorithms for estimating pre-test probability of disease in symptomatic patients are established from predominantly outdated data. Based on a data synthesis, they define premenopausal women without diabetes as generally at low risk. Only in selected cases based on clinical judgment does the committee recommend further noninvasive testing; if it is performed, the routine exercise ECG is recommended.
The committee takes a clinically practical approach to risk stratification. Women aged 50 years and older accrue a higher pre-test probability. If a woman aged between 50 and 60 years is symptomatic yet can perform activities of daily living, the guideline defines her as low to intermediate risk. If she is functionally limited in activities of daily living, an intermediate to high pre-test probability is assigned. Symptomatic women aged 60 to 70 years are at intermediate pre-test probability of disease, while symptomatic women aged 70 years and older are also at high risk.
Known atherosclerosis in other vascular beds and poorly controlled diabetes at age 40 years and older would both be considered high-risk equivalent conditions in symptomatic women. At any level of risk, the presence of multiple CV risk factors or the inability to perform activities of daily living would add one level of incremental risk.
Recommendations for low-risk, symptomatic women
In general, the guideline update does not recommend testing for low-risk symptomatic women. Low-intermediate and intermediate-risk symptomatic women should have an exercise ECG only if the rest ECG is interpretable, with the addition of stress perfusion imaging if the ECG is uninterpretable. Coronary CT angiography could be considered as an alternative if radiation exposure at the performing center is expected to be low (ie, <3 mSv). Interestingly, while the panel cited impressive prognostic data highlighting the presence of nonobstructive atherosclerosis as an important marker of increased risk, it gives a fairly weak recommendation for CT angiography (IIB recommendation). For symptomatic women at high pre-test risk for disease, a stress perfusion or treadmill stress echo test could be performed to assess ischemic burden and target possible revascularization strategy.
Parag H. Joshi
The guideline committee next makes the point that treatment strategies can be targeted to those symptomatic women with evidence of myocardial ischemia on noninvasive testing. Those women with ischemic symptoms, myocardial ischemia on noninvasive testing, yet nonobstructive coronary disease on angiography, are a population not well represented in randomized controlled trials.
More data to come
The ISCHEMIA-WISE trial will investigate the role of aggressive medical therapy in more than 2,000 men and women with nonobstructive CAD but demonstrable ischemia on stress testing.
Pending that trial, which will take years to carry out and analyze, the guideline update committee recommends utilization of an aggressive anti-ischemic, risk factor-reduction medical regimen in such patients. When imaging with CT angiography is performed before stress testing, and nonobstructive disease is present, the panel does not delineate a clear therapeutic plan except to deem three-vessel nonobstructive disease or a coronary artery calcium score >400 as high risk.
In sum, this guideline update provides an important summary on the role of noninvasive testing in symptomatic women with suspected ischemic heart disease. Ongoing trials will provide important data on the care of this large, challenging and important group of patients.
For more information:
Mieres JH. Circulation. 2014;doi:10.1161/CIR.0000000000000061.
Thomas S. Metkus Jr., MD Fellow; Roger S. Blumenthal, MD; and Parag H. Joshi, MD, are from the Johns Hopkins Ciccarone Center for the Prevention of Heart Disease. Blumenthal is the Cardiology Today CHD and Prevention Section Editor and Joshi is a member of the Fellows Advisory Board. The authors can be reached at rblument@jhmi.edu.
Disclosure: The authors report no relevant financial disclosures.