Improved Cardiac Risk Assessment With Noninvasive Measures of Coronary Flow Reserve

Abstract

Background Impaired vasodilator function is an early manifestation of coronary artery disease and may precede angiographic stenosis. It is unknown whether non-invasive assessment of coronary vasodilator function in patients with suspected or known coronary artery disease (CAD) carries incremental prognostic significance. Methods and Results 2783 consecutive patients referred for rest/stress PET were followed for a median of 1.4 years (inter-quartile range: 0.7–3.2 years). The extent and severity of perfusion abnormalities were quantified by visual evaluation of myocardial perfusion images (MPI). Rest and stress myocardial blood flow (MBF) were calculated using factor analysis and a 2-compartment kinetic model, and were used to compute coronary flow reserve (CFR=stress/rest MBF). The primary endpoint was cardiac death. Overall 3-year cardiac mortality was 8.0%. The lowest tertile of CFR (<1.5) was associated with a 5.6-fold increase in the risk of cardiac death (95%CI 2.5–12.4, p<0.0001) compared to the highest tertile. Incorporation of CFR into cardiac death risk assessment models resulted in an increase in the c-index from 0.82 (95%CI 0.78–0.86) to 0.84 (95%CI 0.80–0.87, p=0.02) and in a net reclassification improvement (NRI) of 0.098 (95%CI 0.025–0.180). Addition of CFR resulted in correct reclassification of 34.8% of intermediate risk patients (NRI=0.487, 95%CI 0.262–0.731). Corresponding improvements in risk assessment for mortality from any cause were also demonstrated. Conclusions Non-invasive quantitative assessment of coronary vasodilator function using PET is a powerful, independent predictor of cardiac mortality in patients with known or suspected CAD and provides meaningful incremental risk stratification over clinical and gated MPI variables.

Clinical Quantification of Myocardial Blood Flow Using PET: Joint Position Paper of the SNMMI Cardiovascular Council and the ASNC

“…46,49,50,53,[92][93][94] Consistently, patients with more severely reduced stress MBF and MFR are at higher risk than patients with preserved values or modest reductions. An analysis of the relationship between MFR and cardiac mortality suggests an excellent prognosis for an MFR of more than 2 and a steady increase in cardiac mortality for an MFR of less than 2 ( Figure 8).…”

“…Stress-first or stress-only imaging is feasible, but it is not routine practice with quantitative PET. Although several studies have suggested that peak hyperemic MBF is superior to MFR, [45][46][47] most studies have concluded that MFR is more powerful for risk stratification, [48][49][50][51][52][53] perhaps because of decreased variability compared with peak hyperemic MBF. 54 Whether postischemic stunning affects resting MBF with stressfirst imaging has not been well studied.…”

“…51,52,91 • A severely reduced global hyperemic MBF and MFR identify patients at high risk for major adverse cardiovascular events, including death. Although thresholds may vary in different labs using different software, in general an MFR of less than 1.5 should be considered a high-risk feature on MPI PET 46,49,50,53,92,94,98,102 and is associated with an Figure 8. Relationship between MFR and risk of cardiac death.…”

Myocardial perfusion imaging in extreme obesity: Leveraging modern technologies to meet a modern challenge

“…CFR, calculated as the ratio of hyperemic to rest myocardial blood flow, provides a combined physiological measure of large-and small-vessel ischemia, and in the absence of overt CAD, is a marker of coronary microvascular dysfunction. CFR has emerged recently as an important prognostic indicator of cardiovascular risk, and identifies patients at risk for CVD death [18][19][20][21] independently of angiographic disease severity, 22,23 ischemic perfusion defects, LV ejection fraction, or a detectable troponin. 24 In particular, CFR may represent an important component of risk stratification in obesity, 25 which is increasingly recognized to be associated with global microvascular dysfunction.…”

Dynamic SPECT: evolution of a widely available tool for the assessment of coronary flow reserve

“…PET enables quantitative assessment of myocardial blood flow (MBF, in millilitres per gram per minute) and coronary flow reserve (CFR), and quantification with 15 O-water, 13 N-ammonia and recently 82 Rb has been validated over a wide range of blood flows in animal models and humans [1][2][3][4]. Quantitative assessment of MBF has been shown to improve the diagnostic accuracy of conventional MPI with SPECT or PET, to improve cardiac risk assessment and to predict outcome [5][6][7]. Quantitation of MBF enables absolute assessment of myocardial flow and vasodilator reserve without the assumption of a normal reference region [8].…”