γ-Glutamyl Transferase and Long-Term Survival in the SYNTAXES Trial: Is It Just the Liver?

BACKGROUND: Recently, machine learning algorithms have identified preprocedural γ-glutamyl transferase (GGT) as a significant predictor of long-term mortality after coronary revascularization in the SYNTAX (Synergy Between PCI [Percutaneous Coronary Intervention] With Taxus and Cardiac Surgery) trial. The aim of the present study is to investigate the impact of preprocedural GGT on 10-year all-cause mortality in patients with complex coronary artery disease after revascularization. METHODS AND RESULTS: The SYNTAX trial was a randomized trial comparing PCI with coronary artery bypass grafting in 1800 patients with complex coronary artery disease. The present report is a post hoc subanalysis of the SYNTAXES (Synergy Between PCI With Taxus and Cardiac Surgery Extended Survival) trial, an investigator-driven extended 10-year follow-up of the SYNTAX trial. The association between preprocedural GGT and 10-year all-cause mortality was investigated. The mean values of GGT for men and women were 43.5 (SD, 48.5) and 36.4 (SD, 46.1) U/L, respectively. In multivariable Cox regression models adjusted by traditional risk factors, GGT was an independent predictor for all-cause death at 10-year follow-up, and each SD increase in log-GGT was associated with a 1.24-fold risk of all cause death at 10-year follow-up (95% CI, 1.10-1.40). According to previously reported sex-related GGT thresholds, patients with higher GGT level had a 1.74-fold risk of all-cause death at 10-year follow-up (95% CI, 1.32-2.29) compared with patients with lower GGT level. CONCLUSIONS: Preprocedural GGT is an independent predictor of 10-year mortality after coronary revascularization in patients with complex coronary artery disease. In patients with elevated GGT, strong secondary prevention may be required after revascularization and must be studied prospectively. REGISTRATION: URL: https://clinicaltrials.gov/study/NCT03417050.

Coronary bypass surgery guided by computed tomography in a low-risk population.

BACKGROUND AND AIMS: In patients with three-vessel disease and/or left main disease, selecting revascularization strategy based on coronary computed tomography angiography (CCTA) has a high level of virtual agreement with treatment decisions based on invasive coronary angiography (ICA). METHODS: In this study, coronary artery bypass grafting (CABG) procedures were planned based on CCTA without knowledge of ICA. The CABG strategy was recommended by a central core laboratory assessing the anatomy and functionality of the coronary circulation. The primary feasibility endpoint was the percentage of operations performed without access to the ICA. The primary safety endpoint was graft patency on 30-day follow-up CCTA. Secondary endpoints included topographical adequacy of grafting, major adverse cardiac and cerebrovascular (MACCE), and major bleeding events at 30 days. The study was considered positive if the lower boundary of confidence intervals (CI) for feasibility was ≥75% (NCT04142021). RESULTS: The study enrolled 114 patients with a mean (standard deviation) anatomical SYNTAX score and Society of Thoracic Surgery score of 43.6 (15.3) and 0.81 (0.63), respectively. Unblinding ICA was required in one case yielding a feasibility of 99.1% (95% CI 95.2%-100%). The concordance and agreement in revascularization planning between the ICA- and CCTA-Heart Teams was 82.9% with a moderate kappa of 0.58 (95% CI 0.50-0.66) and between the CCTA-Heart Team and actual treatment was 83.7% with a substantial kappa of 0.61 (95% CI 0.53-0.68). The 30-day follow-up CCTA in 102 patients (91.9%) showed an anastomosis patency rate of 92.6%, whilst MACCE was 7.2% and major bleeding 2.7%. CONCLUSIONS: CABG guided by CCTA is feasible and has an acceptable safety profile in a selected population of complex coronary artery disease.

Prasugrel Monotherapy After Percutaneous Coronary Intervention for Chronic Coronary Syndrome: Insights From ASET Pilot Studies.

Background: The ASET (Acetyl-Salicylic Elimination Trial) pilot studies recently investigated P2Y12 inhibitor monotherapy without aspirin immediately after percutaneous coronary intervention (PCI) in Brazil and Japan. Objectives: This comparative analysis of the 2 ASET pilot studies aimed to summarize clinical outcomes and assess geographic and ethnic differences in baseline demographics and procedures. Methods: Patients undergoing successful platinum-chromium everolimus-eluting stent implantation for chronic coronary syndrome were included. Following the index PCI, patients received prasugrel monotherapy with a maintenance dose of 10 mg/day in Brazil and 3.75 mg/day in Japan. The primary ischemic endpoint was the composite of cardiac death, spontaneous target vessel myocardial infarction, or definite stent thrombosis. The primary bleeding endpoint was Bleeding Academic Research Consortium types 3 and 5 bleeding at up to 3 months. Results: Of 409 enrollments, 3-month follow-up was completed in 406 patients. Mean age was 64.3 ± 8.4 years, and 73% were men. Overall, post-TIMI flow grade 3 was achieved in 99.8%. Intravascular imaging for poststent optimization was used in 16.8% and 99.6% of treated lesions in Brazil and Japan, respectively. The primary ischemic and bleeding endpoints occurred in the same patient (0.2%). No stent thrombosis events occurred. Conclusions: Prasugrel monotherapy following PCI was safe and feasible in selected low-risk chronic coronary syndrome patients after optimal platinum-chromium everolimus-eluting stent implantation regardless of the ethnic and geographic differences in baseline demographics, procedures, and prasugrel dosage. Randomized controlled trials will be needed to compare P2Y12 inhibitor monotherapy without aspirin with the current standard of care.

Five-year outcomes in patients with multivessel coronary artery disease undergoing surgery or percutaneous intervention.

The outcomes from real-life clinical studies regarding the optimal revascularization strategy in patients with multivessel coronary artery disease (MVD) are still poorly investigated. In this retrospective study we assessed 5-year outcomes: primary, secondary endpoints and quality of life of 1035 individuals with severe coronary artery disease (CAD) treated either with coronary artery bypass grafting (CABG)-356 patients or percutaneous coronary intervention (PCI)-679 patients according to the recommendation of a local Heart Team (HT). At 5 years no significant difference in overall mortality and rates of myocardial infarctions (MI) were observed between CABG and PCI cohorts (11.0% vs. 13.4% for PCI, P = 0.27 and 9.6% vs. 12.8% for PCI, P = 0.12, respectively). The incidence of major adverse cardiac and cerebrovascular events (MACCE), mainly driven by increased rates of repeat revascularization (RR) were higher in PCI-cohort than in CABG-group (56.1% vs. 40.4%, P < 0.01 and 26.8% vs. 12.6%, P < 0.01, respectively), while CABG-patients experienced stroke more often (7.3% vs. 3.1% for PCI, P < 0.01). In real-life practice with long-term follow-up, none of the two revascularization modalities implemented following HT decisions showed overwhelming superiority: occurrence of death and MI were similar, rates of RR favoured CABG, while incidence of strokes advocated PCI.

Percutaneous Alginate Hydrogel Endomyocardial Injection with a Novel Dedicated Catheter Delivery System: An Animal Feasibility Study.

The objective of this preclinical study was to evaluate the feasibility and safety of transcatheter endocardial alginate hydrogel injection (TEAi) in a large animal model, utilizing the high-stiffness XDROP® alginate hydrogel in combination with the dedicated EndoWings® catheter-based system. All swine (n = 9) successfully underwent TEAi without complications. Acute results from a subset of animals (n = 5) demonstrated the ability of the catheter to access a wide range of endomyocardial areas and achieve consecutive circumferential hydrogel distribution patterns within the mid-left ventricular wall. Histological examinations at 6 months (n = 4) demonstrated that the XDROP® remained localized within the cardiac tissue. In addition, serial echocardiographic imaging showed that XDROP® had no adverse impacts on LV systolic and diastolic functions. In conclusion, this innovative combination technology has the potential to overcome the translational barriers related to alginate hydrogel delivery to the myocardium.

Randomized evaluation of 5-month Ticagrelor monotherapy after 1-month dual-antiplatelet therapy in patients with acute coronary syndrome treated with drug-coated balloons: REC-CAGEFREE II trial rationale and design.

BACKGROUND: Patients treated with drug-coated balloons (DCB) have the theoretical advantage of adopting a low-intensity antiplatelet regimen due to the absence of struts and polymers. Nevertheless, the optimal antiplatelet strategy for patients undergoing DCB-only treatment remains a topic of debate and has not been investigated in randomized trials. METHODS: The REC-CAGEFREE II is an investigator-initiated, prospective, open-label, multi-center, randomized, non-inferiority trial aimed to enroll 1908 patients from ≥ 40 interventional cardiology centers in China to evaluate the non-inferiority of an antiplatelet regimen consisting of Aspirin plus Ticagrelor for one month, followed by five months Ticagrelor monotherapy, and then Aspirin monotherapy for six months (Experimental group) compared to the conventional treatment of Aspirin plus Ticagrelor for 12 months (Reference group) in patients with acute coronary syndrome (ACS) who have undergone percutaneous coronary intervention (PCI) using paclitaxel-coated balloons (DCB) exclusively. Participants will be randomly assigned to the Experimental or Reference group in a 1:1 ratio. The randomization will be stratified based on the center and the type of lesion being treated (De novo or in-stent restenosis). The primary endpoint is net adverse clinical events (NACE) within 12 months of PCI, which includes the composite of all-cause death, any stroke, any myocardial infarction, any revascularization and Bleeding Academic Research Consortium (BARC) defined type 3 or 5 bleeding. The secondary endpoint, any ischemic and bleeding event, which includes all-cause death, any stroke, MI, BARC-defined type 3 bleeding, any revascularization, and BARC-defined type 2 bleeding events, will be treated as having hierarchical clinical importance in the above order and analyzed using the win ratio method. DISCUSSION: The ongoing REC-CAGEFREE II trial aims to assess the efficacy and safety of a low-intensity antiplatelet approach among ACS patients with DCB. If non-inferiority is shown, the novel antiplatelet approach could provide an alternative treatment for ACS patients with DCB. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT04971356.

Geographic disparity of pathophysiological coronary artery disease characteristics: Insights from ASET trials.

BACKGROUND: The geographical disparity in the pathophysiological pattern of coronary artery disease (CAD) among patients undergoing percutaneous coronary intervention (PCI) is unknown. OBJECTIVES: To elucidate the geographical variance in the pathophysiological characteristics of CAD. METHODS: Physiological indices derived from angiography-based fractional flow reserve pullbacks from patients with chronic coronary syndrome enrolled in the ASET Japan (n = 206) and ASET Brazil (n = 201) studies, which shared the same eligibility criteria, were analysed. The pathophysiological patterns of CAD were characterised using Murray law-based quantitative flow ratio (µQFR)-derived indices acquired from pre-PCI angiograms. The diffuseness of CAD was defined by the µQFR pullback pressure gradient index. RESULTS: Significant functional stenoses pre-PCI (µQFR ≤0.80) were more frequent in ASET Japan compared to ASET Brazil (89.9% vs. 67.5%, p < 0.001), as were rates of a post-PCI µQFR <0.91 (22.1% vs. 12.9%, p = 0.013). In the multivariable analysis, pre-procedural µQFR and diffuse disease were independent factors for predicting a post-PCI µQFR <0.91, which contributed to the different rates of post-PCI µQFR ≥0.91 between the studies. Among vessels with a post-PCI µQFR <0.91, a consistent diffuse pattern of CAD pre- and post-PCI occurred in 78.3% and 76.7% of patients in ASET Japan and Brazil, respectively; only 6.3% (Japan) and 10.0% (Brazil) of vessels had a major residual gradient. Independent risk factors for diffuse disease were diabetes mellitus in ASET Japan, and age and male gender in Brazil. CONCLUSIONS: There was geographic disparity in pre-procedural angiography-based pathophysiological characteristics. The combined pre-procedural physiological assessment of vessel µQFR and diffuseness of CAD may potentially identify patients who will benefit most from PCI.

Feasibility and accuracy of real-time 3D-holographic graft length measurements.

Aims: Mixed reality (MR) holograms can display high-definition images while preserving the user's situational awareness. New MR software can measure 3D objects with gestures and voice commands; however, these measurements have not been validated. We aimed to assess the feasibility and accuracy of using 3D holograms for measuring the length of coronary artery bypass grafts. Methods and results: An independent core lab analyzed follow-up computer tomography coronary angiograms performed 30 days after coronary artery bypass grafting in 30 consecutive cases enrolled in the FASTTRACK CABG trial. Two analysts, blinded to clinical information, performed holographic reconstruction and measurements using the CarnaLife Holo software (Medapp, Krakow, Poland). Inter-observer agreement was assessed in the first 20 cases. Another analyst performed the validation measurements using the CardIQ W8 CT system (GE Healthcare, Milwaukee, Wisconsin). Seventy grafts (30 left internal mammary artery grafts, 31 saphenous vein grafts, and 9 right internal mammary artery grafts) were measured. Holographic measurements were feasible in 97.1% of grafts and took 3 minutes 36 s ± 50.74 s per case. There was an excellent inter-observer agreement [interclass correlation coefficient (ICC) 0.99 (0.97-0.99)]. There was no significant difference between the total graft length on hologram and CT [187.5 mm (157.7-211.4) vs. 183.1 mm (156.8-206.1), P = 0.50], respectively. Hologram and CT measurements are highly correlated (r = 0.97, P < 0.001) with an excellent agreement [ICC 0.98 (0.97-0.99)]. Conclusion: Real-time holographic measurements are feasible, quick, and accurate even for tortuous bypass grafts. This new methodology can empower clinicians to visualize and measure 3D images by themselves and may provide insights for procedural strategy.

Murray law-based quantitative flow ratio to assess left main bifurcation stenosis: selecting the angiographic projection matters.

Murray law-based quantitative flow ratio (µQFR) assesses fractional flow reserve (FFR) in bifurcation lesions using a single angiographic view, enhancing the feasibility of analysis; however, accuracy may be compromised in suboptimal angiographic projections. FFRCT is a well-validated non-invasive method measuring FFR from coronary computed tomographic angiography (CCTA). We evaluated the feasibility of µQFR in left main (LM) bifurcations, the impact of the optimal/suboptimal fluoroscopic view with respect to CCTA, and its diagnostic concordance with FFRCT. In 300 patients with three-vessel disease, the values of FFRCT and µQFR were compared at distal LM, proximal left anterior descending artery (pLAD) and circumflex artery (pLCX). The optimal viewing angle of LM bifurcation was defined on CCTA by 3-dimensional coordinates and converted into a 2-dimensional fluoroscopic view. The best fluoroscopic projection was considered the closest angulation to the optimal viewing angle on CCTA. µQFR was successfully computed in 805 projections. In the best projections, µQFR sensitivity was 88.2% (95% CI 76.1-95.6) and 84.8% (71.1-93.7), and specificity was 96.8% (93.8-98.6) and 97.2% (94.4-98.9), in pLAD and pLCX, respectively, with regard to FFRCT. The AUC of µQFR for predicting FFRCT ≤ 0.80 tended to be improved using the best versus suboptimal projections (0.94 vs. 0.89 [p = 0.048] in pLAD; 0.94 vs. 0.88 [p = 0.075] in pLCX). Computation of µQFR in LM bifurcations using a single angiographic view showed high feasibility from post-hoc analysis of coronary angiograms obtained for clinical purposes. The fluoroscopic viewing angle influences the diagnostic performance of physiological assessment using a single angiographic view.

Impact of left ventricular ejection fraction on 10-year mortality in the SYNTAX trial.

BACKGROUNDS: The impact of reduced left ventricular ejection fraction (LVEF) on very long-term prognosis following percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) has been debated. The aim of this study was to investigate the impact of LVEF at baseline on 10-year mortality in the SYNTAX trial. METHODS: Patients (n = 1800) were categorized into three sub-groups: reduced (rEF ≤ 40 %), mildly reduced (mrEF 41-49 %), and preserved LVEF (pEF ≥ 50 %). The SYNTAX score 2020 (SS-2020) was applied in patients with LVEF<50 % and ≥ 50 %. RESULTS: Ten-year mortalities were 44.0 %, 31.8 %, and 22.6 % (P < 0.001) in patients with rEF (n = 168), mrEF (n = 179), and pEF (n = 1453). Although no significant differences were observed, the mortality with PCI was higher than with CABG in patients with rEF (52.9 % vs 39.6 %, P = 0.054) and mrEF (36.0 % vs. 28.6 %, P = 0.273), and comparable in pEF (23.9 % vs. 22.2 %, P = 0.275). Calibration and discrimination of the SS-2020 in patients with LVEF<50 % were poor, whilst they were reasonable in those with LVEF≥50 %. The proportion of patients eligible for PCI who had a predicted equipoise in mortality with CABG was estimated to be 57.5 % in patients with LVEF≥50 %. CABG was safer than PCI in 62.2 % of patients with LVEF<50 %. CONCLUSIONS: Reduced LVEF was associated with an increased risk of 10-year mortality in patients revascularized either surgically or percutaneously. Compared to PCI, CABG was safe revascularization in patients with LVEF≤40 %. In patients with LVEF≥50 % individualized 10-year all-cause mortality predicted by SS-2020 was helpful in decision-making whilst the predictivity in patients with LVEF<50 % was poor.