Temporal changes in PET myocardial flow reserve: Implications for cardiovascular outcomes

The usefulness of serial measurements of myocardial flow reserve (MFR) has received limited study outside of transplant vasculopathy. We describe the trends of myocardial blood flow and perfusion over time in patients undergoing positron emission tomography (PET) myocardial perfusion imaging (MPI) for the evaluation of coronary artery disease, and their association with cardiovascular outcomes.

We retrospectively analyzed data from 474 patients without a history of heart transplant who underwent serial PET MPI (N = 948 studies) for the evaluation of coronary artery disease at Yale New Haven Hospital between 2016 and 2022. Patients were categorized according to MFR trajectory (low to low, low to high, high to low, high to high). Long-term major adverse cardiovascular events (MACE), defined as death or myocardial infarction, were analyzed with the Kaplan-Meier method and Cox regression. Log-likelihood, C-statistic and net reclassification were used to assess model performance.

The median interval time between tests was 776 days (IQR: 497-1058). The most common indications for the first and second PET were chest pain and dyspnea. MFR was similar in serial exams (2.1 [1.7, 2.6] vs 2.1 [1.7, 2.5], P = .75), but rest (1 [.8, 1.3] vs .9 [.7, 1] P < .01) and stress flows (2.1 [1.6, 2.8] vs 1.8 [1.4, 2.2], P < .01) were both reduced on the second PET. MFR increased in patients with revascularization between tests (N = 62 patients) (1.6 [1.3, 2.0] vs 1.7 [1.2, 2.2], P = .04). During a median follow-up time of 17 [8,28] months, the rate of MACE was 12% (51 events) and was higher in the low-to-low and low-to-high categories in multivariable analysis. The model including serial MFR and perfusion performed better than the baseline model including traditional clinical risk factors in terms of the likelihood ratio and C-statistic (from .74 to .80, P = .04).

In conclusion, our findings suggest that the serial assessment of MFR and perfusion may improve risk stratification beyond traditional clinical risk factors.