TransCatheter aortic valve implantation and fractional flow reserve-guided percutaneous coronary intervention versus conventional surgical aortic valve replacement and coronary bypass grafting for treatment of patients with aortic valve stenosis and multivessel or advanced coronary disease: The transcatheter valve and vessels trial (TCW trial): Design and rationale.

BACKGROUND: Patients with severe aortic stenosis (AS) frequently present with concomitant obstructive coronary artery disease (CAD). In those, current guidelines recommend combined coronary artery bypass grafting (CABG) and surgical aortic valve replacement (SAVR) as the preferred treatment option, although this surgical approach is associated with a high rate of clinical events. Combined transcatheter aortic valve implantation (TAVI) and percutaneous coronary intervention (PCI) with or without FFR have evolved as a valid alternative for cardiac surgery in patients with AS and multivessel or advanced CAD. To date, no dedicated trial has prospectively evaluated the outcomes of a percutaneous versus surgical treatment for patients with both severe AS and CAD. AIMS: To investigate whether fractional-flow reserve (FFR)-guided PCI and TAVI is noninferior to combined CABG and SAVR for the treatment of severe AS and multivessel or advanced CAD. METHODS: The Transcatheter Valve and Vessels (TCW) trial (clinicaltrial.gov: NCT03424941) is a prospective, randomized, controlled, open label, international trial. Patients ≥ 70 years with severe AS and multivessel (≥ 2 vessels) or advanced CAD, deemed feasible by the heart team for both; a full percutaneous or surgical treatment, will be randomised in a 1:1 fashion to either FFR-guided PCI followed by TAVI (intervention arm) vs. CABG and SAVR (control arm). The primary endpoint is a patient-oriented composite of all-cause mortality, myocardial infarction, disabling stroke, unscheduled clinically-driven target vessel revascularization, valve reintervention, and life threatening or disabling bleeding at 1 year. The TCW trial is powered for noninferiority, and if met, superiority will be tested. Assuming a primary endpoint rate of 30% in the CABG-SAVR arm, with a significance level α of 5%, a noninferiority limit delta of 15% and a loss to follow-up of 2%, a total of 328 patients are needed to obtain a power of 90%. The primary endpoint analysis is performed on an intention-to-treat basis. SUMMARY: The TCW Trial is the first prospective randomized trial that will study if a less invasive percutaneous treatment for severe AS and concomitant advanced CAD (i.e., FFR-guided PCI-TAVI) is noninferior to the guidelines recommended approach (CABG-SAVR).

Fractional Flow Reserve-Guided Deferred Versus Complete Revascularization in Patients With Diabetes Mellitus.

To assess the safety and efficacy of deferred versus complete revascularization using a fractional flow reserve (FFR)-guided strategy in patients with diabetes mellitus (DM), we analyzed all DM patients who underwent FFR-guided revascularization from January 1, 2010, to December 12, 2013. Patients were divided into 2 groups: those with ≥1 remaining FFR-negative (>0.80) medically treated lesions [FFR(-)MT] and those with only FFR-positive lesions (≤0.80) who underwent complete revascularization [FFR(+)CR] and were followed until July 1, 2015. The primary end point was the incidence of major adverse cardiovascular events (MACE), a composite of death, myocardial infarction (MI), target lesion (FFR assessed) revascularization, and rehospitalization for acute coronary syndrome. A total of 294 patients, 205 (69.7%) versus 89 (30.3%) in FFR(-)MT and FFR(+)CR, respectively, were analyzed. At a mean follow-up of 32.6 ± 18.1 months, FFR(-)MT was associated with higher MACE rate 44.0% versus 26.6% (log-rank p = 0.02, Cox regression-adjusted hazard ratio [HR] 2.01, 95% confidence interval [CI] 1.21 to 3.33, p <0.01), and driven by both safety and efficacy end points: death/MI (HR 2.02, 95% CI 1.06 to 3.86, p = 0.03), rehospitalization for acute coronary syndrome (HR 2.06, 95% CI 1.03 to 4.10, p = 0.04), and target lesion revascularization (HR 3.38, 95% CI 1.19 to 9.64, p = 0.02). Previous MI was a strong effect modifier within the FFR(-)MT group (HR 1.98, 95% CI 1.26 to 3.13, p <0.01), whereas this was not the case in the FFR(+)CR group (HR 0.66, 95% CI 0.27 to 1.62, p = 0.37). Significant interaction for MACE was present between FFR groups and previous MI (p = 0.03). In conclusion, in patients with DM, particularly those with previous MI, deferred revascularization is associated with poor medium-term outcomes. Combining FFR with imaging techniques may be required to guide our treatment strategy in these patients with high-risk, fast-progressing atherosclerosis.

Clinical outcomes of deferred revascularisation using fractional flow reserve in patients with and without diabetes mellitus.

OBJECTIVE: Deferred revascularisation based upon fractional flow reserve (FFR >0.80) is associated with a low incidence of target lesion failure (TLF). Whether deferred revascularisation is also as safe in diabetes mellitus (DM) patients is unknown. METHODS: All DM patients and the next consecutive Non-DM patients who underwent a FFR-assessment between 1/01/2010 and 31/12/2013 were included, and followed until 1/07/2015. Patients with lesions FFR >0.80 were analysed according to the presence vs. absence of DM, while patients who underwent index revascularisation in FFR-assessed or other lesions were excluded. The primary endpoint was the incidence of TLF; a composite of target lesion revascularisation (TLR) and target vessel myocardial infarction (TVMI). RESULTS: A total of 250 patients (122 DM, 128 non-DM) who underwent deferred revascularisation of all lesions (FFR >0.80) were compared. At a mean follow up of 39.8 ± 16.3 months, DM patients compared to non-DM had a higher TLF rate, 18.1 vs 7.5 %, logrank p ≤ 0.01, Cox regression-adjusted HR 3.65 (95 % CI 1.40-9.53, p < 0.01), which was largely driven by a higher incidence of TLR (17.2 vs. 7.5 %, HR 3.52, 95 % CI 1.34-9.30, p = 0.01), whilst a non-significant but numerically higher incidence of TVMI (6.1 vs. 2.0 %, HR 3.34, 95 % CI 0.64-17.30, p = 0.15) was observed. CONCLUSIONS: This study, the largest to directly compare the clinical outcomes of FFR-guided deferred revascularisation in patients with and without DM, shows that DM patients are associated with a significantly higher TLF rate. Whether intravascular imaging, additional invasive haemodynamics or stringent risk factor modification may impact on this higher TLF rate remains unknown.