Coronary Atherosclerotic Plaque Activity and Future Coronary Events

Abstract

ImportanceRecurrent coronary events in patients with recent myocardial infarction remain a major clinical problem. Noninvasive measures of coronary atherosclerotic disease activity have the potential to identify individuals at greatest risk.ObjectiveTo assess whether coronary atherosclerotic plaque activity as assessed by noninvasive imaging is associated with recurrent coronary events in patients with myocardial infarction.Design, Setting, and ParticipantsThis prospective, longitudinal, international multicenter cohort study recruited participants aged 50 years or older with multivessel coronary artery disease and recent (within 21 days) myocardial infarction between September 2015 and February 2020, with a minimum 2 years’ follow-up.InterventionCoronary 18F-sodium fluoride positron emission tomography and coronary computed tomography angiography.Main Outcomes and MeasuresTotal coronary atherosclerotic plaque activity was assessed by 18F-sodium fluoride uptake. The primary end point was cardiac death or nonfatal myocardial infarction but was expanded during study conduct to include unscheduled coronary revascularization due to lower than anticipated primary event rates.ResultsAmong 2684 patients screened, 995 were eligible, 712 attended for imaging, and 704 completed an interpretable scan and comprised the study population. The mean (SD) age of participants was 63.8 (8.2) years, and most were male (601 [85%]). Total coronary atherosclerotic plaque activity was identified in 421 participants (60%). After a median follow-up of 4 years (IQR, 3-5 years), 141 participants (20%) experienced the primary end point: 9 had cardiac death, 49 had nonfatal myocardial infarction, and 83 had unscheduled coronary revascularizations. Increased coronary plaque activity was not associated with the primary end point (hazard ratio [HR], 1.25; 95% CI, 0.89-1.76; P = .20) or unscheduled revascularization (HR, 0.98; 95% CI, 0.64-1.49; P = .91) but was associated with the secondary end point of cardiac death or nonfatal myocardial infarction (47 of 421 patients with high plaque activity [11.2%] vs 19 of 283 with low plaque activity [6.7%]; HR, 1.82; 95% CI, 1.07-3.10; P = .03) and all-cause mortality (30 of 421 patients with high plaque activity [7.1%] vs 9 of 283 with low plaque activity [3.2%]; HR, 2.43; 95% CI, 1.15-5.12; P = .02). After adjustment for differences in baseline clinical characteristics, coronary angiography findings, and Global Registry of Acute Coronary Events score, high coronary plaque activity was associated with cardiac death or nonfatal myocardial infarction (HR, 1.76; 95% CI, 1.00-3.10; P = .05) but not with all-cause mortality (HR, 2.01; 95% CI, 0.90-4.49; P = .09).Conclusions and RelevanceIn this cohort study of patients with recent myocardial infarction, coronary atherosclerotic plaque activity was not associated with the primary composite end point. The findings suggest that risk of cardiovascular death or myocardial infarction in patients with elevated plaque activity warrants further research to explore its incremental prognostic implications.

Can Noncalcified Plaques Contribute to Future Coronary Events?—Reply

“…We have demonstrated the feasibility of using coronary 18 F-sodium fluoride to add incremental value to traditional risk prediction scores in patients at very high risk of plaque rupture . By performing hybrid contrast enhanced coronary CT angiography in our study, we have shown that coronary 18 F-sodium fluoride was associated with an increased risk of cardiac death and nonfatal myocardial infarction after adjustment for internationally endorsed CT parameters (adjusted hazard ratio, 1.78; 95% CI, 1.03-3.06; P = .04).…”

“…In contrast, 18 F-sodium fluoride offers a promising solution to monitor the slow progressive transition from a noncalcified to calcified phenotype noted by intense 18 F-sodium fluoride signals persisting more than 12 months . Unlike the transient vascular signals observed with inflammatory radioligands, there is minimal attenuation of the 18 F-sodium fluoride signal with optimal medical therapy—a potential explanation for why patients with increased coronary 18 F-sodium fluoride remain at increased risk of cardiac death and myocardial infarction in the medium term . To our knowledge, our work represents the first prospective observational cohort using coronary positron emission tomography, but complementary prospective observational studies to discern the predictive ability of radioligands measuring vascular inflammation with 18 F-fluoro-2-deoxyglucose and 68 Ga-DOTATATE are ongoing.…”

“…In Reply We thank Erbay and colleagues for their interest in our recent work regarding atherosclerotic plaque characterization using coronary 18 F-sodium fluoride positron emission tomography . They ask a timely question—does the monitoring of disease activity with target-specific radioligands provide additional clinical value beyond the quantitative anatomical assessment afforded by coronary computed tomography (CT) angiography?…”

18F-NaF Uptake on Vascular PET Imaging in Symptomatic versus Asymptomatic Atherosclerotic Disease: a Meta-Analysis

“…Studies have also demonstrated a correlation between NaF uptake and high-risk morphological features on MRI, such as the presence of a lipid-rich necrotic core, or intraplaque haemorrhage 39 . In addition, there is emerging evidence of a prognostic link between NaF signal on PET and the risk of recurrent disease 40 , where coronary NaF imaging had the ability to predict myocardial infarction and cardiovascular death.…”

Can Noncalcified Plaques Contribute to Future Coronary Events?

“…To the Editor Moss et al recently published a prospective, international, multicenter longitudinal cohort study of 704 patients with recent myocardial infarction (MI) that investigated whether coronary atherosclerotic plaque activity as assessed by 18 F-sodium fluoride positron emission tomography (PET) and coronary computed tomography (CT) angiography is associated with recurrent coronary events. Their findings suggest that coronary atherosclerotic plaque activity is not associated with cardiac death, nonfatal MI, or revascularization after a minimum 2-year follow-up period.…”