الفهرس 
Radiological AnatomyOnly 14 pages are availabe for public view
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Abstract
Coronary revascularization is often performed on an ad hoc basis from semi-quantitative measures of percent luminal diameter narrowing of the artery visualized at the time of invasive coronary angiography (ICA). This practice stems from the research of Gould et al., who elegantly demonstrated the relationship between stenosis and ischemia, as determined by myocardial blood flow reserve, wherein flow to the myocardium is compromised as the luminal diameter progressively narrows. This diminution in flow is most evident at hyperemic states and begins as early as 40% narrowing of vessel diameter, with more predictable reductions in hyperemic flow for stenoses > 70% (Taylor et al., 2013).
However, the relationship between coronary stenosis and myocardial ischemia is more complex, with ensuing studies demonstrating an unreliable relationship between stenosis and ischemia. One example of this was highlighted in the nuclear substudy of the COURAGE (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation) trial; in this study in patients with ≥ 70% stenosis, only 32% exhibited severe ischemia and 40% manifested no or mild ischemia according to myocardial perfusion scintigraphy (Shaw et al., 2008).
At present, the gold standard assessment of the hemodynamic significance of coronary stenoses is fractional flow reserve (FFR). FFR uses a pressure wire to determine the ratio of maximal coronary blood flow through a stenotic artery to the blood flow in the hypothetical case that the artery was normal, and it is the only diagnostic method to date for ischemia detection to demonstrably advance event free survival (Taylor et al., 2013).
In the FAME (Fractional Flow Reserve Versus Angiography for Multivessel Evaluation) trial of 1,005 patients with multivessel coronary artery disease (CAD), FFR-guided revascularization (i.e, revascularization for lesions with
FFR ≤ 0.80) was associated with a 28% lower rate of major adverse cardiac events compared with an angiography-guided strategy. The salutary outcomes for individuals undergoing FFR-guided revascularization are long-lived and cost-saving (Tonino et al., 2009).
The results from FAME are in accordance with the 5-year follow-up of individuals from the DEFER (Deferral Versus Performance of PTCA in Patients without Documented Ischemia) study (Taylor et al., 2013).
Among lesions judged angiographically “obstructive,”
> 50% were hemodynamically insignificant according to FFR. No benefit was observed for revascularization in patients with hemodynamically insignificant lesions. In the FAME2 trial, FFR-guided therapy reduced the need for urgent revascularization in patients with stable CAD and hemo-dynamically significant lesions (De Bruyne et al., 2012).
Coronary computed tomography angiography (CTA) is a noninvasive method for visualization of CAD. Previous CTA studies have observed an overestimation of stenosis severity, and even among high-grade stenoses according to CTA confirmed by using ICA, only a minority cause ischemia. Coronary lesions considered severe according to CTA cause ischemia less than one-half of the time. These findings have provoked concerns that widespread application of CTA may encourage unnecessary ICA (Taylor et al., 2013).
Numerous imaging tests exist for physiological assessment of CAD, including stress echocardiography, cardiac magnetic resonance, and myocardial perfusion scintigraphy. These modalities assess wall motion abnormalities or regional differences in coronary flow reserve (CFR) as a surrogate for ischemia and identify individuals who may have severe stenoses. Although robust for ischemia detection on a per-patient basis, these tests demonstrate poor discrimination of specific vessels with coronary lesions that cause ischemia. As an example, when using an FFR standard for vessel-specific ischemia, myocardial perfusion scintigraphy identifies ischemic territories correctly < 50% of the time, with underestimation and overestimation in 36% and 22% of cases, respectively (Taylor et al., 2013).
Such data have evoked concerns for the ability of stress testing to effectively isolate coronary lesions that benefit from revascularization. Recent advances in computational fluid dynamics enable calculation of coronary flow and pressure fields from anatomic image data. Applied to CTA, these technologies enable calculation of FFR without additional imaging or medications (Taylor et al., 2013).
The DISCOVER-FLOW (Diagnosis of Ischemia-Causing Stenoses Obtained Via Noninvasive Fractional Flow Reserve) trial, compared with invasive FFR, noninvasive FFR derived from CTA, or FFRCTA, demonstrated per-vessel accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for lesions causing ischemia of 84.3%, 87.9%, 82.2%, 73.9%, and 92.2%, respectively, for FFRCTA. The performance of FFRCTA was superior to CTA stenosis for diagnosing ischemic lesions, the latter of which demonstrated an accuracy, sensitivity, specificity, PPV, and NPV of 58.5%, 91.4%, 39.6%, 46.5%, and 88.9%, respectively (Koo et al., 2011).
More recently, the DeFACTO (Determination of Fractional Flow Reserve by Anatomic Computed Tomographic Angiography) trial, a pivotal multicenter international study evaluating FFRCTA against CTA for diagnostic accuracy of ischemia, has been published. This trial consisted of 252 patients for which 407 vessels were directly interrogated by using FFR. On a per-patient basis, FFRCTA was superior to CTA stenosis for diagnosis of ischemic lesions for accuracy (73% vs. 64%), sensitivity (90% vs. 84%), specificity (54% vs. 42%), PPV (67% vs. 61%), and NPV (84% vs. 72%). In patients with intermediate stenoses (30% to 70%), there was a more than 2-fold increase in sensitivity, from 37% to 82%, with no loss of specificity (Min et al., 2012).
The result of the most recent study in the evaluation of FFR CT ; NXT (Analysis of Coronary Blood Flow Using CT Angiography: Next Steps) trial; published in April 2014 has revealed the high diagnostic performance of FFR CT compared with invasively measured FFR, identifying patients with hemodynamically relevant obstructions with high sensitivity and specificity. Compared with anatomic interpretation by using coronary CTA, FFR CT led to a marked increase in diagnostic specificity. The addition of FFR CT to coronary CTA may allow for a comprehensive anatomic and functional assessment of CAD in a manner potentially promoting beneficial clinical and cost outcomes, which remain to be definitively proven in appropriately designed prospective trials (Nørgaard et al., 2014).
Computational Fluid Dynamics (CFD) methods applied to CTA data may also enable prediction of changes in coronary flow and pressure from therapeutic interventions (e.g., percutaneous coronary intervention, coronary artery bypass graft) FFRCTA enables study of other hemodynamic metrics (e.g., CFR, shear stress, total plaque force). In addition, other physiological states such as graded exercise conditions can be modeled. Finally, the technology underlying FFRCTA is applicable to other common cardiovascular conditions, including peripheral, cerebrovascular, and renovascular disease, and may be used to determine whether vascular stenoses are hemodynamically significant as well as the relative benefit of therapeutic interventions (Taylor et al., 2013).