title: 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: COMBINE (OCT-FFR) prospective study. Rationale and design.
abstract: Fractional flow reserve (FFR) is a widely used tool for the identification of ischaemia-generating stenoses and to guide decisions on coronary revascularisation. However, the safety of FFR-based decisions in high-risk subsets, such as patients with Diabetes Mellitus (DM) or vulnerable stenoses presenting thin-cap fibro-atheroma (TCFA), is unknown. This study will examine the impact of optical coherence tomography (OCT) plaque morphological assessment and the identification of TCFA, in combination with FFR to better predict clinical outcomes in DM patients.
  
  
  
  COMBINE (OCT-FFR) is a prospective, multi-centre study investigating the natural history of DM patients with ≥1 angiographically intermediate target lesion in three subgroups of patients; patients with FFR negative lesions without TCFA (group A) and patients with FFR negative lesions with TCFA (group B) as detected by OCT and to compare these two groups with each other, as well as to a third group with FFR-positive, PCI-treated intermediate lesions (group C). The study hypothesis is that DM patients with TCFA (group B) have a worse outcome than those without TCFA (group A) and also when compared to those patients with lesions FFR ≤0.80 who underwent complete revascularisation. The primary endpoint is the incidence of target lesion major adverse cardiac events (MACE); a composite of cardiac death, myocardial infarction or rehospitalisation for unstable/progressive angina in group B vs. group A.
  
  
  
  COMBINE (OCT-FFR) is the first prospective study to examine whether the addition of OCT plaque morphological evaluation to FFR haemodynamic assessment of intermediate lesions in DM patients will better predict MACE and possibly lead to new revascularisation strategies. Trial Registration Netherlands Trial Register: NTR5376.
authors.affiliation: Isala Hartcentrum, Docter van Heesweg 2, Zwolle, The Netherlands.|Diagram CRO, Zwolle, The Netherlands.
authors.forename: Mark W
authors.initials: MW
authors.lastname: Kennedy
authors.affiliation: Isala Hartcentrum, Docter van Heesweg 2, Zwolle, The Netherlands.|Diagram CRO, Zwolle, The Netherlands.
authors.forename: Enrico
authors.initials: E
authors.lastname: Fabris
authors.affiliation: Albert Schweitzer Ziekenhuis, Dordrecht, The Netherlands.
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: Ijsselmuiden
authors.affiliation: University of Giessen, Giessen, Germany.
authors.forename: Holger
authors.initials: H
authors.lastname: Nef
authors.affiliation: University Hospital of the RWTH Aachen, Aachen, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Reith
authors.affiliation: Hospital Clinico San Carlos, Madrid, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Escaned
authors.affiliation: Hospital Universitario de La Princesa, Madrid, Spain.
authors.forename: Fernando
authors.initials: F
authors.lastname: Alfonso
authors.affiliation: VU University Medical Centre, Amsterdam, The Netherlands.
authors.forename: Niels
authors.initials: N
authors.lastname: van Royen
authors.affiliation: Medical University of Silesia, Katowice, Poland.
authors.forename: Wojtek
authors.initials: W
authors.lastname: Wojakowski
authors.affiliation: Institute of Cardiology, Warsaw, Poland.
authors.forename: Adam
authors.initials: A
authors.lastname: Witkowski
authors.affiliation: Azienda Ospedaliera Universitaria Materdomini, Catanzaro, Italy.
authors.forename: Ciro
authors.initials: C
authors.lastname: Indolfi
authors.affiliation: Isala Hartcentrum, Docter van Heesweg 2, Zwolle, The Netherlands.
authors.forename: Jan Paul
authors.initials: JP
authors.lastname: Ottervanger
authors.affiliation: Isala Hartcentrum, Docter van Heesweg 2, Zwolle, The Netherlands.|Diagram CRO, Zwolle, The Netherlands.|Radboud University Medisch Centrum, Nijmegen, The Netherlands.
authors.forename: Harry
authors.initials: H
authors.lastname: Suryapranata
authors.affiliation: Isala Hartcentrum, Docter van Heesweg 2, Zwolle, The Netherlands. e.kedhi@isala.nl.|Diagram CRO, Zwolle, The Netherlands. e.kedhi@isala.nl.
authors.forename: Elvin
authors.initials: E
authors.lastname: Kedhi
mesh_terms: D006328:Cardiac Catheterization; D002985:Clinical Protocols; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000503:physiopathology / Q000628:therapy; D023921:Coronary Stenosis / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000503:physiopathology / Q000628:therapy; D003331:Coronary Vessels / Q000000981:diagnostic imaging* / Q000503:physiopathology*; D003925:Diabetic Angiopathies / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000503:physiopathology / Q000628:therapy; D018450:Disease Progression; D005060:Europe; D053805:Fractional Flow Reserve, Myocardial; D006439:Hemodynamics; D006801:Humans; D062645:Percutaneous Coronary Intervention; D058226:Plaque, Atherosclerotic; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012107:Research Design; D012720:Severity of Illness Index; D013997:Time Factors; D041623:Tomography, Optical Coherence; D016896:Treatment Outcome
keywords: Diabetes mellitus; Fractional flow reserve; Major adverse cardiac event