A multi-center, international, randomized, 2-year, parallel-group study to assess the superiority of IVUS-guided PCI versus qualitative angio-guided PCI in unprotected left main coronary artery (ULMCA) disease: Study protocol for OPTIMAL trial

Background Percutaneous coronary intervention (PCI) is used increasingly for revascularization of unprotected left main coronary artery (LMCA) disease. Observational studies and subgroup analyses from clinical trials, have suggested a possible benefit from the use of intravascular ultrasound (IVUS) guidance when performing unprotected LMCA PCI. However, the value of imaging with IVUS has never been proven in an appropriately powered randomized clinical trial. The OPtimizaTIon of Left MAin PCI With IntravascuLar Ultrasound (OPTIMAL) trial has been designed to establish whether IVUS-guided PCI optimization on LMCA is associated with superior clinical outcomes when compared with standard qualitative angiography-guided PCI. Methods The OPTIMAL trial is a randomized, multicenter, international study designed to enroll a total of 800 patients undergoing PCI for unprotected LMCA disease. Patients will be randomized in a 1:1 fashion to IVUS-guided PCI versus angiogram-guided PCI. In patients allocated to the angiogram-guided arm, use of IVUS is discouraged, unless there are safety concerns. In patients allocated to the IVUS guidance arm, pre-procedural IVUS assessment is highly recommended, whilst post-procedural IVUS assessment is mandatory to confirm appropriate stenting result and/or to guide stent result optimization, according to predefined criteria. Patients will be followed up to 2 years after the index procedure. The primary outcome measure is the Academic Research Consortium (ARC) patient-oriented composite endpoint (PoCE) which includes all-cause death, any stroke, any myocardial infarction and any repeat revascularization at 2 years follow-up. Discussion The OPTIMAL trial aims to provide definitive evidence about the clinical impact of IVUS-guidance during PCI to an unprotected LMCA. It is anticipated by the investigators, that an IVUS-guided strategy will be associated with less clinical events compared to a strategy guided by angiogram alone. Trial registration ClinicalTrials.gov: NCT04111770. Registered on October 1, 2019.

Percutaneous catheter-based repeat revascularization in patients with previous PCI or CABG: a comprehensive review of the evidence

Repeat revascularization after percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) is one of the most common long-term complications which warrants continuous clinical follow up. Re-interventions negatively impact long-term survival in patients with coronary artery disease. The repeat revascularization after PCI can be either a target lesion revascularization (stent thrombosis/in-stent restenosis) or a revascularization of native coronary artery after PCI (target vessel revascularization/non-target vessel revascularization). The EVENT registry reports that repeat revascularization rates in patients undergoing PCI is 12% in the first year of follow up. Repeat revascularization with additional stent deployment increases the rate of stent thrombosis and restenosis, thereby leading to recurrent ischemic events. Repeat revascularization after CABG can be either in the early postoperative period or later due to native disease progression or late graft stenosis. The need for re-intervention after surgical or percutaneous revascularization is inevitable and is dependent on modifiable and non-modifiable risk factors.

A Simple Model to Predict Repeat Revascularization After Drug-Eluting Stent Implantation in Patients With Stable Coronary Artery Disease

Repeat revascularization is still common in the era of drug-eluting stents (DES), especially for non-target lesions. However, few validated models exist to predict the need for revascularization. We aimed to develop and validate an easy-to-use predictive model for repeat revascularization after DES implantation in patients with stable coronary artery disease (CAD). A total of 1,653 stable CAD patients with angiographic follow-up after DES implantation were consecutively enrolled. Split-sample testing was adopted to develop and validate the model. In the training set, male, diabetes, number of target lesions, occlusion lesion, number of non-target lesions, recurrent angina, suboptimal low density lipoprotein-cholesterol level, and high lipoprotein (a) level were independent predictors of repeat revascularization using logistic regression analyses. The established model (Model 1) yielded a bias-corrected concordance index of 0.700 (95% confidence interval: 0.667 to 0.735), with good calibration. It also performed well in the validation set. Compared with the traditional empirical model only including recurrent angina (Model 2), Model 1 had better discriminative ability and clinical usefulness. In conclusion, we established and validated a simple model including 8 easily accessible variables to predict repeat revascularization after DES implantation in stable CAD patients, contributing to better risk stratification, decision making, and patient consultation.

Comparison of Clinically Adjudicated Versus Flow-Based Adjudication of Revascularization Events in Randomized Controlled Trials

Background: In clinical trials, the optimal method of adjudicating revascularization events as clinically or nonclinically indicated (CI) is to use an independent Clinical Events Committee (CEC). However, the Academic Research Consortium-2 currently recommends using physiological assessment. The level of agreement between these methods of adjudication remains unknown. Methods: Data for all CEC adjudicated revascularization events among the 3457 patients followed-up for 2-years in the TALENT trial, and 3-years in the DESSOLVE III, PIONEER, and SYNTAX II trial were collected and readjudicated according to a quantitative flow ratio (QFR) analysis of the revascularized vessels, by an independent core lab blinded to the results of the conventional CEC adjudication. The κ statistic was used to assess the level of agreement between the 2 methods. Results: In total, 351 CEC-adjudicated repeat revascularization events occurred, with retrospective QFR analysis successfully performed in 212 (60.4%). According to QFR analysis, 104 events (QFR ≤0.80) were adjudicated as CI revascularizations and 108 (QFR >0.80) were not. The agreement between CEC and QFR based adjudication was just fair (κ=0.335). Between the 2 methods of adjudication, there was a disagreement of 26.4% and 7.1% in CI and non-CI revascularization, respectively. Overall, the concordance and discordance rates were 66.5% and 33.5%, respectively. Conclusions: In this event-level analysis, QFR based adjudication had a relatively low agreement with CEC adjudication with respect to whether revascularization events were CI or not. CEC adjudication appears to overestimate CI revascularization as compared with QFR adjudication. Direct comparison between these 2 strategies in terms of revascularization adjudication is warranted in future trials. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: TALENT trial: NCT02870140, DESSOLVE III trial: NCT02385279, SYNTAX II: NCT02015832, and PIONEER trial: NCT02236975.

Stress testing-guided assessment of coronary artery bypass grafts patency, at 6 months of follow up. A prospective study

Purpose: To assess the coronary bypass grafts patency and the repeat revascularization rate, six months after coronary artery bypass grafting (CABG). Methods: We prospectively enrolled 145 consecutive patients undergoing isolated CABG between June 2014 and June 2016. We performed at 6 months of follow up a coronary computed tomography angiography (CTA) in patients whose stress tests were negative and an invasive coronary angiography (ICA) in the opposite case. Results: A total of 134 CTA and 11 ICA were performed, allowing the analysis of 321 grafts, including 143 left internal thoracic arteries (LITA), 89 right internal thoracic arteries (RITA) and 89 saphenous veins grafts (SVG). The average graft patency was 95.1% for LITA, 84.3% for RITA and 64% for SVG. The best patencies were obtained when these grafts were anastomosed to the left anterior descending artery (LAD): 96.3% for LITA, and 87.5% for RITA. SVG patency was homogeneous whether between the main right coronary artery and its branches (63.4% versus 65% respectively. p = 1), or between circumflex and RCA (72.7% versus. 63.9% respectively. p=0.6). On the right and circumflex coronary arteries, the patency of the SVG was significantly lower than that of RITA (66.26% versus 83.95% respectively, p = 0.011). At 6 months of follow up, the repeat revascularization rate was 2.07% (n=3/145). Conclusions: 6 months after CABG, RITA and LITA had good patencies especially on LAD, while SVG was occluded in almost a third of cases. On the circumflex and right coronary arteries, SVG patency was significantly lower than that of RITA. Keywords: Coronary Artery Bypass; Exercise Testing; Coronary Angiography; Computed Tomography Angiograph

Long‐Term (7‐Year) Clinical Implications of Newly Unveiled Asymptomatic Abnormal Ankle–Brachial Index in Patients With Coronary Artery Disease

Background The long‐term impact of newly discovered, asymptomatic abnormal ankle–brachial index (ABI) in patients with significant coronary artery disease is limited. Methods and Results Between January 2006 and December 2009, ABI was evaluated in 2424 consecutive patients with no history of claudication or peripheral artery disease who had significant coronary artery disease. We previously reported a 3‐year result; therefore, the follow‐up period was extended. The primary end point was a composite of all‐cause death, myocardial infarction (MI), and stroke over 7 years. Of the 2424 patients with significant coronary artery disease, 385 had an abnormal ABI (ABI ≤0.9 or ≥1.4). During the follow‐up period, the rate of the primary outcome was significantly higher in the abnormal ABI group than in the normal ABI group ( P <0.001). The abnormal ABI group had a significantly higher risk of composite of all‐cause death/MI/stroke than the normal ABI group, after adjustment with multivariable Cox proportional hazards regression analysis (hazard ratio [HR], 2.07; 95% CI, 1.67–2.57; P <0.001) and propensity score–matched analysis (HR, 1.97; 95% CI, 1.49–2.60; P <0.001). In addition, an abnormal ABI was associated with a higher risk of all‐cause death, MI, and stroke, but not repeat revascularization. Conclusions Among patients with significant coronary artery disease, asymptomatic abnormal ABI was associated with sustained and increased incidence of composite of all‐cause death/MI/stroke, all‐cause death, MI, and stroke during extended follow‐up over 7 years.

Repeat revascularization impact on 10-year survival after PCI or CABG: post-hoc analysis of the SYNTAXES trial

Background Available data comparing Percutaneous Coronary Interventions (PCI) and Coronary Artery Bypass Graft (CABG) in multivessel or left main coronary artery disease (CAD) suggest higher rates of repeat revascularization events after PCI than CABG, with a negative influence on outcomes up to 5 years. The impact of repeat revascularization on very long-term outcomes remains unclear. Aims This study aims to investigate the impact on 10-year all-cause death of repeat revascularizations in patients with three-vessel disease (3VD) and/or left main coronary artery disease (LMCAD). Methods The SYNTAXES study evaluated the vital status out to 10-year of patients with 3VD and/or LMCAD enrolled in the SYNTAX trial. Repeat revascularization events occurred within the first 5 years from the index procedure were adjudicated by an independent clinical events committee. Effects of repeat revascularizations on 10-year all-cause death were investigated through time-dependent Cox regression analysis. Results During the first 5 years, 330 out of 1800 patients (18.3%) underwent a minimum of one repeat revascularization, for a total of 459 repeat revascularization procedures, mostly consisting of repeat-PCI (393, 85.6%). Repeat revascularizations were more frequent among patients initially randomized to PCI (HR 2.3, 95% CI: 1.8–3.0, p&lt;0.0001). At 10 years, all-cause death was comparable between patients underwent any repeat revascularization and those not (27.6% vs. 25.1%, adjusted HR 2.3, 95% CI: 0.8–6.2, p=0.11). However, among patients requiring repeat revascularizations, who underwent initial PCI versus initial CABG presented a significantly higher 10-year all-cause death (32.7% vs 17.3%, p=0.004). The adjusted risk for 10-year all-cause death according to the subtypes of repeat revascularizations revealed only revascularization with CABG was an independent predictor (HR 6.2, 95% CI: 1.5–25.2, p=0.011). Conclusions In the SYNTAX trial, repeat revascularizations were more frequent after initial PCI. Although no difference on 10-year all-cause death was observed between patients who did undergo repeat revascularizations and who did not, higher death rates were reported among those required any repeat procedures after initial PCI or revascularization with CABG. These exploratory findings should be investigated with larger population in future studies. FUNDunding Acknowledgement Type of funding sources: None. Survival curves at 10-year follow-up