Thin-Cap Fibroatheroma Rather Than Any Lipid Plaques Increases the Risk of Cardiovascular Events in Diabetic Patients: Insights From the COMBINE OCT–FFR Trial

Abstract

Background: Autopsy studies have established that thin-cap fibroatheromas (TCFAs) are the most frequent cause of fatal coronary events. In living patients, optical coherence tomography (OCT) has sufficient resolution to accurately differentiate TCFA from thick-cap fibroatheroma (ThCFA) and not lipid rich plaque (non-LRP). However, the impact of OCT-detected plaque phenotype of nonischemic lesions on future adverse events remains unknown. Therefore, we studied the natural history of OCT-detected TCFA, ThCFA, and non-LRP in patients enrolled in the prospective multicenter COMBINE FFR-OCT trial (Combined Optical Coherence Tomography Morphologic and Fractional Flow Reserve Hemodynamic Assessment of Non-Culprit Lesions to Better Predict Adverse Event Outcomes in Diabetes Mellitus Patients). Methods: In the COMBINE FFR-OCT trial, patients with diabetes and ≥1 lesion with a fractional flow reserve >0.80 underwent OCT evaluation and were clinically followed for 18 months. A composite primary end point of cardiac death, target vessel-related myocardial infarction, target-lesion revascularization, and hospitalization for unstable angina was evaluated in relation to OCT-based plaque morphology. Results: A total of 390 patients (age 67.5±9 years; 63% male) with ≥1 nonischemic lesions underwent OCT evaluation: 284 (73%) had ≥1 LRP and 106 (27%) non-LRP lesions. Among LRP patients, 98 (34.5%) had ≥1 TCFA. The primary end point occurred in 7% of LRP patients compared with 1.9% of non-LRP patients (7.0% versus 1.9%; hazard ratio [HR], 3.9 [95% CI, 0.9–16.5]; P =0.068; log rank- P =0.049). However, within LRP patients, TCFA patients had a much higher risk for primary end point compared with ThCFA (13.3% versus 3.8%; HR, 3.8 [95% CI, 1.5–9.5]; P <0.01), and to non-LRP patients (13.3% versus 1.9%; HR, 7.7 [95% CI, 1.7–33.9]; P <0.01), whereas ThCFA patients had risk similar to non-LRP patients (3.8% versus 1.9%; HR, 2.0 [95% CI, 0.42–9.7]; P =0.38). Multivariable analyses identified TCFA as the strongest independent predictor of primary end point (HR, 6.79 [95% CI, 1.50–30.72]; P =0.013). Conclusions: Among diabetes patients with fractional flow reserve-negative lesions, patients carrying TCFA lesions represent only one-third of LRP patients and are associated with a high risk of future events while patients carrying LRP-ThCFA and non-LRP lesions portend benign outcomes. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02989740.

Morphometric Assessment for Functional Evaluation of Coronary Stenosis with Optical Coherence Tomography and the Optical Flow Ratio in a Vessel with Single Stenosis

“…FFR only provides the value of coronary hemodynamics, cannot show detailed anatomical information of vessels and does not objectively identify vessel conditions with high-risk characteristics, such as erosive plaque, thin cap fibro atheroma (TCFA) and the vulnerable plaque of lesions. It has been pointed out that about 20% of lesions with FFR > 0.80 have high-risk characteristics under OCT, such as thin cap fibro atheroma [ 17 , 18 ]. Although TCFA has not yet led to hemodynamics changes, it is still a powerful predictor of major adverse cardiovascular events [ 17 , 18 ].…”

“…It has been pointed out that about 20% of lesions with FFR > 0.80 have high-risk characteristics under OCT, such as thin cap fibro atheroma [ 17 , 18 ]. Although TCFA has not yet led to hemodynamics changes, it is still a powerful predictor of major adverse cardiovascular events [ 17 , 18 ]. Therefore, with the aim of optimizing the PCI, intracoronary imaging, such as OCT, with a high resolution, can accurately identify the TCFA [ 19 ], which makes up for the FFR deficiencies.…”

Transcoronary stem cell transfer and evolution of infarct-related artery atherosclerosis: evaluation with conventional and novel imaging techniques including Quantitative Virtual Histology (qVH)

“…Intravascular imaging plays a fundamental role in longitudinal studies of atherosclerosis evolution [45][46][47][48][49][50], including evaluation of plaque morphology (and its changes) in relation to atherosclerosis-mediated cardiac adverse clinical events such as MI and cardiac death [48,[51][52][53][54]. Intracoronary imaging is particularly important for its increased accuracy (against traditional planar analysis of intraarterial angiography images) of lesion detection and evaluation of its severity and morphology.…”

Exploring new insights in coronary lesion assessment and treatment in patients with diabetes mellitus: the impact of optical coherence tomography

“…Therefore, OCT is currently the most accurate method for visualising and measuring the thickness of the fibrotic cap and thus detecting true TCFAs [ 60 ]. The relevance of this feature is paramount, as was also demonstrated in a substudy of the COMBINE OCT-FFR trial in which lipid-rich plaques were common but less likely to be associated with adverse cardiac events in the absence of TCFAs [ 61 ]. In this sense, OCT may substantially narrow the number of patients who might benefit from a more aggressive novel treatment.…”