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

Mark W Kennedy, Enrico Fabris, Alexander J Ijsselmuiden, Holger Nef, Sebastian Reith, Javier Escaned, Fernando Alfonso, Niels van Royen, Wojtek Wojakowski, Adam Witkowski, Ciro Indolfi, Jan Paul Ottervanger, Harry Suryapranata, Elvin Kedhi, Mark W Kennedy, Enrico Fabris, Alexander J Ijsselmuiden, Holger Nef, Sebastian Reith, Javier Escaned, Fernando Alfonso, Niels van Royen, Wojtek Wojakowski, Adam Witkowski, Ciro Indolfi, Jan Paul Ottervanger, Harry Suryapranata, Elvin Kedhi

Abstract

Background: 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.

Methods: 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.

Conclusion: 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.

Trial registration: ClinicalTrials.gov NCT02989740.

Keywords: Diabetes mellitus; Fractional flow reserve; Major adverse cardiac event.

Figures

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Fig. 1
Study flow-chart

References

    1. The Emerging Risk Factors Collaboration Diabetes mellitus, fasting blood glucose concentration, and risk of vascular disease: a collaborative meta-analysis of 102 prospective studies. Lancet. 2010;375:2215–2222. doi: 10.1016/S0140-6736(10)60484-9.
    1. Goraya TY, Leibson CL, Palumbo PJ, Weston SA, Killian JM, Pfeifer EA, Jacobsen SJ, Frye RL, Roger VL. Coronary atherosclerosis in diabetes mellitus a population-based autopsy study. J Am Coll Cardiol. 2002;40(5):946–953. doi: 10.1016/S0735-1097(02)02065-X.
    1. Kolh P, Windecker S, Alfonso F, Collet JP, Cremer J, Falk V, Filippatos G, Hamm C, Head SJ, Jüni P, Kappetein AP. 2014 ESC/EACTS guidelines on myocardial revascularization the task force on myocardial revascularization of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS) developed with the special contribution of the European Association of Percutaneous Cardiovascular Interventions (EAPCI) Euro J Cardio-Thorac Surg. 2014;46(4):517–592. doi: 10.1093/ejcts/ezu366.
    1. Tonino PA, De Bruyne B, Pijls NH, Siebert U, et al. Fractional flow reserve versus angiography for guiding percutaneous coronary intervention. N Engl J Med. 2009;360(3):213–224. doi: 10.1056/NEJMoa0807611.
    1. De Bruyne B, Pijls NH, Kalesan B, Barbato E, Tonino PA, Piroth Z, Jagic N, Mobius-Winkler S, Rioufol G, Witt N, et al. Fractional flow reserve-guided PCI versus medical therapy in stable coronary disease. N Engl J Med. 2012;367(11):991–1001. doi: 10.1056/NEJMoa1205361.
    1. Pijls NH, Schaardenburgh P, Manoharan G, Boersma E, et al. Percutaneous coronary intervention of functionally nonsignificant stenosis: 5-year follow-up of the DEFER Study. J Am Coll Cardiol. 2007;49(21):2105–2111. doi: 10.1016/j.jacc.2007.01.087.
    1. Liu Z, Matsuzawa Y, Herrmann J, Li J, Lennon RJ, Crusan DJ, Kwon TG, Zhang M, Sun T, Yang S, et al. Relation between fractional flow reserve value of coronary lesions with deferred revascularization and cardiovascular outcomes in non-diabetic and diabetic patients. Int J Cardiol. 2016;219:56–62. doi: 10.1016/j.ijcard.2016.05.032.
    1. Kennedy MW, Kaplan E, Hermanides RS, Fabris E, Hemradj V, Koopmans PC, Dambrink JH, Marcel Gosselink AT, Van’t Hof AW, Ottervanger JP, et al. Clinical outcomes of deferred revascularisation using fractional flow reserve in patients with and without diabetes mellitus. Cardiovasc Diabetol. 2016;15:100. doi: 10.1186/s12933-016-0417-2.
    1. Kennedy MW, Kaplan E, Hermanides RS, Fabris E, Hemradj V, Koopmans PC, Dambrink JH, et al. Fractional flow reserve guided deferred versus complete revascularization in patients with diabetes mellitus. Am J Cardiol. 2016
    1. Lee JM, Jung J-H, Hwang D, Park J, Fan Y, Na S-H, Doh J-H, Nam C-W, Shin E-S, Koo B-K. Coronary flow reserve and microcirculatory resistance in patients with intermediate coronary stenosis. J Am Coll Cardiol. 2016;67(10):1158–1169. doi: 10.1016/j.jacc.2015.12.053.
    1. Beckman J, Creager M, Libby P. Diabetes and atherosclerosis: epidemiology, pathophysiology, and management. JAMA. 2002;287(19):2570–2581. doi: 10.1001/jama.287.19.2570.
    1. Kanter JE, Johansson F, LeBoeuf RC, Bornfeldt KE. Do glucose and lipids exert independent effects on atherosclerotic lesion initiation or progression to advanced plaques? Circ Res. 2007;100(6):769–781. doi: 10.1161/01.RES.0000259589.34348.74.
    1. Stone GW, Maehara A, Lansky AJ, de Bruyne B, Cristea E, Mintz GS, Mehran R, McPherson J, Farhat N, Marso SP, et al. A prospective natural-history study of coronary atherosclerosis. N Engl J Med. 2011;364(3):226–235. doi: 10.1056/NEJMoa1002358.
    1. Kedhi E, Kennedy MW, Maehara A, Lansky AJ, et al. Impact of TCFA on unanticipated ischemic events in medically treated diabetes mellitus: insights from the PROSPECT study. J Am Coll Cardiol Img. 2016
    1. Marso SP, Mercado N, Maehara A, Weisz G, Mintz GS, McPherson J, Schiele F, Dudek D, Fahy M, Xu K, et al. Plaque composition and clinical outcomes in acute coronary syndrome patients with metabolic syndrome or diabetes. J Am Coll Cardiol Img. 2012;5(3 Suppl):S42–S52. doi: 10.1016/j.jcmg.2012.01.008.
    1. Kato K, Yonetsu T, Kim SJ, Xing L, Lee H, McNulty I, Yeh RW, Sakhuja R, Zhang S, Uemura S, et al. Comparison of nonculprit coronary plaque characteristics between patients with and without diabetes: a 3-vessel optical coherence tomography study. J Am Coll Cardiol Interv. 2012;5(11):1150–1158. doi: 10.1016/j.jcin.2012.06.019.
    1. Waksman R, Legutko J, Singh J, Orlando Q, Marso S, Schloss T, Tugaoen J, DeVries J, Palmer N, Haude M, et al. FIRST: fractional flow reserve and intravascular ultrasound relationship study. J Am Coll Cardiol. 2013;61(9):917–923. doi: 10.1016/j.jacc.2012.12.012.
    1. Lopez PR, Carrillo P, Agudo P, Frutos A, Cordero A, López MA, Ramos D. Correlation between intracoronary ultrasound and fractional flow reserve in long coronary lesions A three-dimensional intracoronary ultrasound study. Rev Esp Cardiol (Engl Ed) 2013;66(9):707–714. doi: 10.1016/j.recesp.2013.04.024.
    1. Cho Y-K, Nam C-W, Han J-K, Koo B-K, Doh J-H, Ben-Dor I, Waksman R, Pichard A, Murata N, Tanaka N, et al. Usefulness of combined intravascular ultrasound parameters to predict functional significance of coronary artery stenosis and determinants of mismatch. EuroIntervention. 2015;11:163–170. doi: 10.4244/EIJV11I2A30.
    1. Gutierrez-Chico JL, Alegria-Barrero E, Teijeiro-Mestre R, Chan PH, Tsujioka H, de Silva R, Viceconte N, Lindsay A, Patterson T, Foin N, et al. Optical coherence tomography: from research to practice. Eur Heart J Cardiovasc Imaging. 2012;13(5):370–384. doi: 10.1093/ehjci/jes025.
    1. Gonzalo N, Escaned J, Alfonso F, Nolte C, Rodriguez V, Jimenez-Quevedo P, Banuelos C, Fernandez-Ortiz A, Garcia E, Hernandez-Antolin R, et al. Morphometric assessment of coronary stenosis relevance with optical coherence tomography: a comparison with fractional flow reserve and intravascular ultrasound. J Am Coll Cardiol. 2012;59(12):1080–1089. doi: 10.1016/j.jacc.2011.09.078.
    1. Fujii K, Kawasaki D, Masutani M, Okumura T, Akagami T, Sakoda T, Tsujino T, Ohyanagi M, Masuyama T. OCT assessment of thin-cap fibroatheroma distribution in native coronary arteries. J Am Coll Cardiol Imaging. 2010;3(2):168–175. doi: 10.1016/j.jcmg.2009.11.004.
    1. Jang IK, Tearney GJ, MacNeill B, Takano M, Moselewski F, Iftima N, Shishkov M, Houser S, Aretz HT, Halpern EF, et al. In vivo characterization of coronary atherosclerotic plaque by use of optical coherence tomography. Circulation. 2005;111(12):1551–1555. doi: 10.1161/01.CIR.0000159354.43778.69.
    1. Bezerra HG, Costa MA, Guagliumi G, Rollins AM, Simon DI. Intracoronary optical coherence tomography: a comprehensive review clinical and research applications. J Am Coll Cardiol Intv. 2009;2(11):1035–1046. doi: 10.1016/j.jcin.2009.06.019.
    1. Nasu K, Tsuchikane E, Katoh O, Fujita H, Surmely JF, Ehara M, Kinoshita Y, Tanaka N, Matsubara T, Asakura Y, et al. Plaque characterisation by Virtual Histology intravascular ultrasound analysis in patients with type 2 diabetes. Heart. 2008;94(4):429–433. doi: 10.1136/hrt.2007.118950.
    1. Nicholls SJ, Tuzcu EM, Kalidindi S, Wolski K, Moon KW, Sipahi I, Schoenhagen P, Nissen SE. Effect of diabetes on progression of coronary atherosclerosis and arterial remodeling: a pooled analysis of 5 intravascular ultrasound trials. J Am Coll Cardiol. 2008;52(4):255–262. doi: 10.1016/j.jacc.2008.03.051.
    1. Reith S, Battermann S, Hoffmann R, Marx N, Burgmaier M. Optical coherence tomography derived differences of plaque characteristics in coronary culprit lesions between type 2 diabetic patients with and without acute coronary syndrome. Catheter Cardiovasc Interv. 2014;84(5):700–707. doi: 10.1002/ccd.25267.
    1. Burgmaier M, Hellmich M, Marx N, Reith S. A score to quantify coronary plaque vulnerability in high-risk patients with type 2 diabetes: an optical coherence tomography study. Cardiovasc Diabetol. 2014;13(1):1. doi: 10.1186/s12933-014-0117-8.
    1. Kedhi E. Netherlands Trial Register: NTR5376: 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 register. . Accessed Nov 22, 2015.
    1. Kedhi E, Généreux P, Palmerini T, et al. Impact of coronary lesion complexity on drug-eluting stent outcomes in patients with and without diabetes mellitus: analysis from 18 pooled randomized trials. J Am Coll Cardiol. 2014;63:2111–2118. doi: 10.1016/j.jacc.2014.01.064.

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