LAUSR

For many decades, stress testing has been at the core of the diagnostic evaluation algorithm for detection of obstructive coronary artery disease (CAD) for the patient presenting with stable, suspected ischemic heart disease.1 The underlying rationale for stress testing is based on the principle of demand ischemia, whereby above a patientspecific exercise workload, myocardial ischemia may be induced in the setting of a functionally limited stenosis. Since the early days of the Master step test, graded exercise with observation of an ischemic threshold has been undertaken to corroborate the patient’s presenting suspected cardiac symptoms and, if positive, to guide anti-ischemic therapy and invasive coronary angiography (ICA) use. The exercise test and knowledge of a given ischemic threshold are fundamental to guiding referral to cardiac rehabilitation, as a basis for exercise prescription, and to guide prescription of anti-ischemic therapies. Depending on the severity of inducible ischemia, the evaluation algorithm may also include referral to ICA and consideration of coronary revascularization, as appropriate.1 For this culminating step in the diagnostic work-up, sufficient inducible ischemia is necessary and forms the basis for ischemia-guided management of stable chest pain. Although straightforward in concept, today’s symptomatic populations are often unable to exercise sufficiently, have a lower prevalence of functionally significant CAD, and often present with atypical symptoms. More than half of referred patients require nonexercise approaches to elucidate ischemia (ie, pharmacologic stress). Obesity and lung disease can impair accurate visualization of ischemia, with image artifact, and may reduce diagnostic accuracy. Moreover, despite the abundant imaging technology to apply during stress testing, localization of ischemia with precise identification of coronary artery stenosis within a given epicardial vessel remains problematic. These factors complicate the diagnostic evaluation and render identification of true ischemia, in the setting of a flow-limiting coronary stenosis, a challenge that requires mastery by the cardiac imager. Over the past decade, noninvasive coronary computed tomographic angiography (CTA) has emerged, with abundant high-quality evidence supporting strong concordance with ICA findings of normal, nonobstructive, and obstructive CAD, and similar clinical effectiveness when compared with functional stress testing.2-4 The randomized trial evidence demonstrate that CTA has a higher diagnostic accuracy when compared with stress testing, often with sensitivity measures more than 90%.1,5 Using CTA-guided management, a large proportion of symptomatic patients without CAD or nonobstructive coronary atherosclerosis do not require additional follow-up. The detection of atherosclerosis serves as a prominent motivator for patients and is associated with improved adherence to cardiovascular preventive care.6,7 This finding has resulted in the UK National Institute for Health and Care Excellence now recommending CTA as the first-line investigation for symptomatic patients, regardless of their pretest CAD likelihood.8 Estimated savings of ~ $20 million US dollars annually were projected following index CTA use within the National Health Services due to the confident exclusion of CAD with CTA and limiting (more costly) stress imaging only to those with obstructive CAD.9 Index evaluation with CTA is, however, challenged by the lack of ischemia evidence and, thus, must currently be coupled selectively with stress testing (in the setting of an intermediate or high grade stenosis). That index CTA testing may lead to prompt referral to ICA without knowledge of provocative ischemia is concerning. Elimination of ischemia testing following CTA is problematic as this evidence guides interventional and medical therapy decisions.1 Ischemia testing, however, may be performed outside of the stress testing laboratory. Intracoronary pressure-derived measurement of fractional flow reserve (FFR) has a robust evidence base in determining lesion-specific ischemia and guiding percutaneous coronary intervention (PCI).10 Based on several clinical trials, selective PCI for stenoses associated with a reduced FFR improves major CAD events when compared with an anatomic-guided interventional approach.11,12 More recent technology now allows for a noninvasive calculation of FFR with CTA (FFR-CT) based on complex computational fluid dynamic modeling to simulate physiologic conditions upon which lesion-specific ischemia may be estimated.13 The controlled clinical trial evidence to date supports a relatively high degree of concordance between invasive and CT-based FFR.14 In this issue of the journal, Cook and colleagues15 provide a systematic review (n = 5 reports in 536 patients) of the FFR-CT evidence with the 82% (overall) diagnostic accuracy threshold met for values of FFR-CT lower than 0.63 or above 0.83. The extremes of FFR-CT values were highly accurate to rule-out (ie, >0.90) or rule-in (ie, ≤0.60) ischemia, as confirmed with Editor's Note