Global Coronary Flow Reserve Is Associated With Adverse Cardiovascular Events Independently of Luminal Angiographic Severity and Modifies the Effect of Early Revascularization
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 (PET), were followed (median 3.1 years) for cardiovascular death and heart failure admission. The extent and severity of angiographic disease was estimated using the CAD prognostic index (CADPI), and CFR measured noninvasively by PET. A modest inverse correlation was seen between CFR and CADPI (r=-0.26, p<0.0001). After adjusting for clinical risk score, ejection fraction, global ischemia, and early revascularization, CFR and CADPI independently associated with events (hazard ratio for unit decrease in CFR, 2.02; 95%CI 1.20-3.40, p=0.008, and for 10-unit increase in CADPI, 1.17; 95%CI 1.01-1.34, p=0.032). Subjects with low CFR experienced rates of events similar to that of subjects with high angiographic scores, and those with low CFR and/or high CADPI showed highest risk of events (p=0.001). There was a significant interaction (p=0.039) between CFR and early revascularization by CABG, such that patients with low CFR who underwent CABG, but not PCI, 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.
- Received June 25, 2014.
- Revision received October 6, 2014.
- Accepted October 16, 2014.