The amount of information gathered in the SYNTAX trial has helped shape both clinical practice and international guidelines in the management of complex coronary artery disease. The conclusions drawn in the SYNTAX trial since its publication do however not take into account areas in which the progress has been made in more contemporary interventional practice.
Some of these progressions are now taken into consideration in the SYNTAX II trial, and discussed below.
A large body of evidence, largely based on the use of fractional flow reserve (FFR), has demonstrated that, compared with angiography, decision making of coronary revascularisation based on physiological assessment of stenosis severity results in improved patient outcomes. Recalculation of the SYNTAX score by incorporating FFR-derived information of stenosis severity (functional SYNTAX score) may decrease the number of higher-risk patients with multivessel disease undergoing PCI and contribute to a better discrimination of risk for adverse events in this subset of patients. A new pressure-derived index, instantaneous wave-free ratio (iFR), that allows faster adenosine-free assessment may be more ideally suited for multiple measurements performed in the context of multivessel disease.
In the SYNTAX II trial iFR/FFR assessment is the first step of the index procedure.
NEWER GENERATION DRUG ELUTING STENT (DES)
Compared to first generation DES, newer generation DES have proven reductions in stent thrombosis and other clinical outcomes. This has largely been through the design of more biocompatible polymers, biodegradable polymers, limus based drugs, thinner stent struts through the incorporation of metallic alloys with greater radial strength, and increased deliverability of the devices. Outcomes of the SYNTAX trial related to newer generation DES are therefore unknown and will now be investigated.
In the SYNTAX II trial the new generation SYNERGY™ and/or SYNERGY II™ DES is used. This DES is designed with thinner struts, biocompatible and biodegradable polymer, and a limus based drug.
IMAGING GUIDANCE OF PCI PROCEDURES
While the proposal of using intravascular ultrasound (IVUS) to tackle restenosis made in the bare metal stent (BMS) era was virtually abandoned with the arrival DES, a growing body of evidence suggests that DES implantation with IVUS guidance in complex anatomical subsets may contribute to better patient outcomes. Specifically, a recent meta-analysis of IVUS guided DES implantation in almost 20,000 subjects has reported significantly reductions in stent thrombosis and mortality.
In the SYNTAX II trial use of IVUS to assess stent deployment is mandatory.
CHRONIC TOTAL OCCLUSION RECANALIZATION
In SYNTAX, the presence of a (chronic) total occlusion (C)TO was identified to be the strongest independent predictor of incomplete revascularisation in the PCI arm of the SYNTAX Trial. Over the last 10 years the practice of (C)TO recanalization has been largely modified by the systematisation in the approach to (C)TO recanalization and the development of new devices. Although acquaintance with these techniques is still limited among interventional cardiologists, international registries have consistently reported that skilled, dedicated (C)TO operators have success rates of 85-95%. This is a much higher success rate that that observed in SYNTAX operators (approximately 50%).
Major technical improvements include the development of new coronary wires, dedicated intracoronary cathethers (Corsair,Ⓡ Tornus,Ⓡ CrossBossTM) and re-entry devices (The Stingray™ CTO Re-Entry System).
Contemporary (C)TO procedures are performed both in anterograde or retrograde fashion (through collateral channels), frequently with the concourse of IVUS imaging. Virtually all these developments were not applied to (C)TO recanalization in SYNTAX.
In the SYNTAX II trial it will therefore be encouraged that each participating centre should select an expert in (C)TO revascularisation who should be involved in the procedure whenever a (C)TO is involved.