Global coronary flow reserve is associated with adverse cardiovascular events independently of luminal angiographic severity and modifies the effect of early revascularization

Abstract

Background: Coronary flow reserve (CFR), an integrated measure of focal, diffuse, and small-vessel coronary artery disease (CAD), identifies patients at risk for cardiac death. We sought to determine the association between CFR, angiographic CAD, and cardiovascular outcomes.

Methods and results: Consecutive patients (n=329) referred for invasive coronary angiography after stress testing with myocardial perfusion positron emission tomography were followed (median 3.1 years) for cardiovascular death and heart failure admission. The extent and severity of angiographic disease were estimated with the use of the CAD prognostic index, and CFR was measured noninvasively by positron emission tomography. A modest inverse correlation was seen between CFR and CAD prognostic index (r=-0.26; P<0.0001). After adjustment for clinical risk score, ejection fraction, global ischemia, and early revascularization, CFR and CAD prognostic index were independently associated with events (hazard ratio for unit decrease in CFR, 2.02; 95% confidence interval, 1.20-3.40; P=0.008; hazard ratio for 10-U increase in CAD prognostic index, 1.17; 95% confidence interval, 1.01-1.34; P=0.032). Subjects with low CFR experienced rates of events similar to those of subjects with high angiographic scores, and those with low CFR or high CAD prognostic index showed the highest risk of events (P=0.001). There was a significant interaction (P=0.039) between CFR and early revascularization by coronary artery bypass grafting, such that patients with low CFR who underwent coronary artery bypass grafting, but not percutaneous coronary intervention, experienced event rates comparable to those with preserved CFR, independently of revascularization.

Conclusions: CFR was associated with outcomes independently of angiographic CAD and modified the effect of early revascularization. Diffuse atherosclerosis and associated microvascular dysfunction may contribute to the pathophysiology of cardiovascular death and heart failure, and impact the outcomes of revascularization.

Keywords: angiography; coronary artery disease; ischemia; positron emission tomography; revascularization.

© 2014 American Heart Association, Inc.

Figures

Figure 1

Association between coronary flow reserve (CFR) and the extent and severity of angiographic disease. A significant but modest inverse correlation (r= −0.26, p

Figure 2

Freedom from cardiovascular death or heart failure admission according to coronary flow reserve (CFR) and angiographic score (CADPI). Freedom from cardiovascular death or heart failure admission differed significantly among subgroups stratified by CFR and CADPI, such that patients with low CFR, independently of angiographic disease score, suffered higher rates of events (overall p=0.03). In adjusted analysis, patients with low CFR experienced rates of events similar to that of patients with high CADPI, and those with low CFR and/or high CADPI showed highest cumulative incidence of events (adjusted overall p=0.001).

Figure 3

Freedom from events according to coronary flow reserve (CFR) and early revascularization. Freedom from cardiovascular death or heart failure admission differed significantly among subgroups stratified by CFR and revascularization (overall log-rank p=0.03, adjusted p=0.002) (A, B). Patients with high CFR, independently of revascularization, experienced lower rates of events, while those with low CFR who did not undergo revascularization suffered the highest rate of events. In the subgroup of patients who underwent revascularization (C, D), there was no difference in event-free survival among those with high CFR (log-rank p=0.76, adjusted p=0.61), but in those with low CFR, only those who also underwent coronary artery bypass grafting, versus percutaneous coronary intervention, experienced lower rates of events (log-rank p=0.02, adjusted p=0.01).

Figure 4

Adjusted annualized rates of cardiovascular death and heart failure admission among patients referred for coronary angiography, by coronary flow reserve (CFR) and early revascularization strategy [coronary artery bypass grafting (CABG), percutaneous coronary intervention (PCI), or neither]. No difference in event rates was seen in patients with high CFR (orange, red, maroon), regardless of revascularization strategy pursued. In patients with low CFR, those who underwent CABG (dark blue) had lower event rates than those who underwent PCI (light blue, p=0.006) or no revascularization (green, p=0.001), and similar event rates to those with high CFR who underwent CABG (maroon). Annualized event rates were adjusted for pretest clinical score, left ventricular ejection fraction, left ventricular ischemia and coronary artery disease prognostic index.