Myocardial perfusion imaging in women for the evaluation of stable ischemic heart disease-state-of-the-evidence and clinical recommendations

Abstract

This document from the American Society of Nuclear Cardiology represents an updated consensus statement on the evidence base of stress myocardial perfusion imaging (MPI), emphasizing new developments in single-photon emission tomography (SPECT) and positron emission tomography (PET) in the clinical evaluation of women presenting with symptoms of stable ischemic heart disease (SIHD). The clinical evaluation of symptomatic women is challenging due to their varying clinical presentation, clinical risk factor burden, high degree of comorbidity, and increased risk of major ischemic heart disease events. Evidence is substantial that both SPECT and PET MPI effectively risk stratify women with SIHD. The addition of coronary flow reserve (CFR) with PET improves risk detection, including for women with nonobstructive coronary artery disease and coronary microvascular dysfunction. With the advent of PET with computed tomography (CT), multiparametric imaging approaches may enable integration of MPI and CFR with CT visualization of anatomical atherosclerotic plaque to uniquely identify at-risk women. Radiation dose-reduction strategies, including the use of ultra-low-dose protocols involving stress-only imaging, solid-state detector SPECT, and PET, should be uniformly applied whenever possible to all women undergoing MPI. Appropriate candidate selection for stress MPI and for post-MPI indications for guideline-directed medical therapy and/or invasive coronary angiography are discussed in this statement. The critical need for randomized and comparative trial data in female patients is also emphasized.

Keywords: ASNC consensus statement; Stable ischemic heart disease; imaging; women.

Figure 1

Diagnostic evaluation algorithm for women presenting with SIHD, from the 2014 consensus statement from the American Heart Association. ADL, activities of daily living; Angio, angiography; DASI, Duke Activity Status Index. Reproduced with permission.

Figure 2

Three-year adjusted rate of cardiac death or myocardial infarction in women (A) and men (B) as a function of ischemia and LVEF. Normal limits of LVEF are ≥51% in women and ≥43% in men. LVEF, left ventricular ejection fraction. Adapted with permission.

Figure 3

Schematic of the ischemic cascade, a sequence of pathophysiologic events associated with CAD, and multi-modality cardiovascular imaging approaches for the evaluation of patients with known or suspected CAD. Anatomy-based and quantitative functional imaging probes earlier events in the cascade than does traditional MPI. This may be especially relevant for the evaluation of women. CCTA, coronary computed tomography angiography; CFR, coronary flow reserve; MPI, myocardial perfusion imaging; SE, stress echocardiography; ETT, exercise treadmill testing. Adapted with permission.

Figure 4

Plots of the predicted CAD mortality per year (and 95% confidence intervals) by the percentage of abnormal myocardial perfusion at stress (A) and by the rest LVEF (B) on ⁸²Rb PET imaging in women and men. An exponential trendline was used to plot CAD mortality for women and men. Reproduced with permission.

Figure 5

Distribution of cardiovascular risk by PET MPI coronary flow reserve (CFR). A CFR value of ≥2 is associated with relatively low rates of annualized cardiac death. Conversely, CFR values<2 are associated with substantially worse prognosis, which may result from vasomotor dysfunction arising from a combination of pathophysiologic CAD phenotypes, including multivessel obstructive CAD, diffuse atherosclerosis, and coronary microvascular dysfunction. Re-produced with permission.

Figure 6

Freedom from cardiovascular death or heart failure admission according to PET MPI coronary flow reserve (CFR) and invasive luminal angiographic score (CAD prognostic index, CADPI). A Patients with very low CFR (<1.6), independently of angiographic disease score, experienced higher rates of events. B In adjusted analysis, patients with very low CFR experienced rates of events similar to those of patients with very high CADPI (>37). PCI percutaneous coronary intervention. CFR denotes coronary flow reserve: high (≥1.6), low (<1.6). CADPI denotes coronary artery disease prognostic index: low (<3.7), high (≥37, reflects >70% stenosis in >1 epicardial artery). Adjusted for pretest clinical score, left ventricular ischemia, and early revascularization with percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG). Early revascularization denotes that within 90 days of noninvasive imaging. Reproduced with permission.

Figure 7

Log adjusted hazard for major adverse cardiovascular events in female versus male patients varies as a function of PET MPI coronary flow reserve. The effect of sex on cardiovascular events was modified by CFR such that differences in outcomes between women and men were amplified for patients with very low CFR, <1.6 (P for interaction = 0.04). CFR, coronary flow reserve; HR, hazard ratio estimated from the linear interaction of CFR and sex. Reproduced with permission.

Figure 8

Relative lifetime cancer risk in men (♂) and women (♀) as a function of age for different myocardial perfusion imaging tracers and protocols. Using Tc-99m instead of ²⁰¹TI SPECT decreases the radiation effective dose (arrows) and cancer risk by a factor of 2. Further reduction by a factor of 2 to 3 is achieved by using current PET tracers. Adapted with permission.

Figure 9

Conceptual model of prevalent pathologic phenotypes in women and men with ischemic heart disease and potential impact on cardiovascular management strategies and outcomes. CABG, coronary artery bypass surgery; CFR, coronary flow reserve; CVD, cardiovascular disease; GDMT, guideline-directed medical therapy; MBF, myocardial blood flow; PCI, percutaneous coronary intervention; VD, vessel disease. Reproduced with permission.

Figure 10

Proposed clinical algorithm for the preferred initial diagnostic evaluation of symptomatic women with suspected stable ischemic heart disease with or without obstructive CAD. *Assumes test is locally available and ALARA principles for radiation dose reduction strategies (i.e., prospective ECG-gated CT, avoidance of dual-isotope and ²⁰¹TI SPECT protocols, and preference for CZT and stress-only SPECT, or PET) are utilized whenever possible. **In cases where an anatomical strategy (i.e., CCTA or invasive coronary angiography) demonstrates absence of obstructive CAD, consider PET-CFR evaluation for coronary microvascular dysfunction. ***If nonobstructive CAD and/or coronary microvascular dysfunction is present, refer for guideline-directed therapies (where paucity of data and guidelines suggests more research is needed to define optimal therapies).

Figure 11

Top Priorities for Cardiovascular Imaging in Women.