Comparative effectiveness of positron emission tomography and single-photon emission computed tomography myocardial perfusion imaging for predicting risk in patients with cardiometabolic disease.

Background: The epidemiology of coronary artery disease (CAD) has shifted, with increasing prevalence of cardiometabolic disease and decreasing findings of obstructive CAD on myocardial perfusion imaging (MPI). Coronary microvascular dysfunction (CMD), defined as impaired myocardial flow reserve (MFR) by positron emission tomography (PET), has emerged as a key mediator of risk. We aimed to assess whether PET MFR provides additive value for risk stratification of cardiometabolic disease patients compared with single-photon emission computed tomography (SPECT) MPI.

Methods: We retrospectively followed patients referred for PET, exercise SPECT, or pharmacologic SPECT MPI with cardiometabolic disease (obesity, diabetes, or chronic kidney disease) and without known CAD. We compared rates and hazards of composite major adverse cardiovascular events (MACEs) (annualized cardiac mortality or acute myocardial infarction) among propensity-matched PET and SPECT patients using Poisson and Cox regression. Normal SPECT was defined as a total perfusion deficit (TPD) of <5%, reflecting the absence of obstructive CAD. Normal PET was defined as a TPD of <5% plus an MFR of ≥2.0.

Results: Among 21,544 patients referred from 2006 to 2020, cardiometabolic disease was highly prevalent (PET: 2308 [67%], SPECT: 9984 [55%]) and higher among patients referred to PET (P < 0.001). Obstructive CAD findings (TPD > 5%) were uncommon (PET: 21% and SPECT: 11%). Conversely, impaired MFR on PET (<2.0) was common (62%). In a propensity-matched analysis over a median 6.4-year follow-up, normal PET identified low-risk (0.9%/year MACE) patients, and abnormal PET identified high-risk (4.2%/year MACE) patients with cardiometabolic disease; conversely, those with normal pharmacologic SPECT remained moderate-risk (1.6%/year, P < 0.001 compared to normal PET).

Conclusions: Cardiometabolic disease is common among patients referred for MPI and is associated with a heterogenous level of risk. Compared with pharmacologic SPECT, PET with MFR can detect nonobstructive CAD including CMD and can more accurately discriminate low-risk from higher-risk individuals.