Enrico Fabris1, Balasz Berta2,3, Tomasz Roleder4, Renicus S Hermanides3, Alexander J J IJsselmuiden5, Floris Kauer6, Fernando Alfonso7, Clemens von Birgelen8,9, Javier Escaned10, Cyril Camaro11, Mark W Kennedy12, Bruno Pereira13, Michael Magro14, Holger Nef15, Sebastian Reith16, Magda Roleder-Dylewska17, Pawel Gasior17, Krzysztof Malinowski18, Giuseppe De Luca19, Hector M Garcia-Garcia20, Juan F Granada21,22, Wojciech Wojakowski17, Elvin Kedhi17,23. 1. Cardiovascular Department, University of Trieste, Italy (E.F.). 2. Heart and Vascular Center, Semmelweis University, Budapest, Hungary (B.B.). 3. Isala Hartcentrum, Zwolle, the Netherlands (B.B., R.S.H.). 4. Department of Cardiology, Hospital Wroclaw, Poland (T.R.). 5. Department of Cardiology, Amphia Ziekenhuis, Breda, the Netherlands (A.J.J.I.). 6. Department of Cardiology, Albert Schweitzer Ziekenhuis, Dordrecht, the Netherlands (F.K.). 7. Department of Cardiology, Hospital Universitario de La Princesa, Madrid, Spain (F.A.). 8. Thoraxcentrum Twente, Medisch Spectrum Twente, Enschede, the Netherlands (C.v.B.). 9. Technical Medical Centre, Health Technology and Services Research, University of Twente, Enschede, Netherlands (C.v.B.). 10. Hospital Clínico San Carlos, Madrid, Spain (J.E.). 11. University Medical Center Radboudumc, Nijmegen, the Netherlands (C.C.). 12. Beaumont Hospital, Dublin, Ireland (M.W.K.). 13. INCCI- Haertz Zenter, Luxembourg (B.P.). 14. Tweesteden Ziekenhuis, Tilburg, the Netherlands (M.M.). 15. Universitätsklinikum, Gießen/Marburg, Germany (H.N.). 16. Uniklinik RWTH, Aachen, Germany (S.R.). 17. Department Medical University of Silesia, Katowice, Poland (M.R.-D., P.G., W.W., E.K.). 18. Department of Bioinformatics and Telemedicine, Faculty of Medicine, Jagiellonian University Medical College, Kraków, Poland (K.M.). 19. Eastern Piedmont University, Novara, Italy (G.D.L.). 20. Interventional Cardiology, MedStar Washington Hospital Center, Washington, D.C. (H.M.G.-G.). 21. Cardiovascular Research Foundation, New York (J.F.G.). 22. Columbia University Medical Center NYC, NY (J.F.G.). 23. Erasmus Hospital, Université Libre de Bruxelles (ULB), Brussels, Belgium (E.K.).
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.
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.