Integrated myocardial flow reserve (iMFR) assessment: diffuse atherosclerosis and microvascular dysfunction are more strongly associated with mortality than focally impaired perfusion

Background and aims: Although treatment of ischemia-causing epicardial stenoses may improve symptoms of ischemia, current evidence does not suggest that revascularization improves survival. Conventional myocardial ischemia imaging does not uniquely identify diffuse atherosclerosis, microvascular dysfunction, or nonobstructive epicardial stenoses. We sought to evaluate the prognostic value of integrated myocardial flow reserve (iMFR), a novel noninvasive approach to distinguish the perfusion impact of focal atherosclerosis from diffuse coronary disease. Methods: This study analyzed a large single-center registry of consecutive patients clinically referred for rest-stress myocardial perfusion positron emission tomography. Cox proportional hazards modeling was used to assess the association of two previously reported and two novel perfusion measures with mortality risk: global stress myocardial blood flow (MBF); global myocardial flow reserve (MFR); and two metrics derived from iMFR analysis: the extents of focal and diffusely impaired perfusion. Results: In total, 6867 patients were included with a median follow-up of 3.4 years [1st–3rd quartiles, 1.9–5.0] and 1444 deaths (21%). Although all evaluated perfusion measures were independently associated with death, diffusely impaired perfusion extent (hazard ratio 2.65, 95%C.I. [2.37–2.97]) and global MFR (HR 2.29, 95%C.I. [2.08–2.52]) were consistently stronger predictors than stress MBF (HR 1.62, 95%C.I. [1.46–1.79]). Focally impaired perfusion extent (HR 1.09, 95%C.I. [1.03–1.16]) was only moderately related to mortality. Diffusely impaired perfusion extent remained a significant independent predictor of death when combined with global MFR (p < 0.0001), providing improved risk stratification (overall net reclassification improvement 0.246, 95%C.I. [0.183–0.310]). Conclusions: The extent of diffusely impaired perfusion is a strong independent and additive marker of mortality risk beyond traditional risk factors, standard perfusion imaging, and global MFR, while focally impaired perfusion is only moderately related to mortality.