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&lt;50 % and ≥ 50 %. Results: Ten-year mortalities were 44.0 %, 31.8 %, and 22.6 % (P &lt; 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&lt;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&lt;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&lt;50 % was poor.</p

10 Years of SYNTAX:Closing an Era of Clinical Research After Identifying New Outcome Determinants

The SYNTAX trial randomized patients equally eligible for coronary artery bypass grafting or percutaneous coronary intervention using the Heart Team approach. The SYNTAXES study achieved a follow-up rate of 93.8% and reported the 10-year vital status. Factors associated with increased mortality at 10 years were pharmacologically treated diabetes mellitus, increased waist circumference, reduced left ventricular function, prior cerebrovascular and peripheral vascular disease, western Europe and North American descent, current smoking, chronic obstructive pulmonary disease, elevated C-reactive protein, anemia, and an increase in HbA1c. Procedural factors associated with higher 10 years mortality include periprocedural myocardial infarction, extensive stenting, small stents, ≥1 heavily calcified lesion, ≥1 bifurcation lesion, residual SYNTAX score &gt;8, and staged percutaneous coronary intervention. Optimal medical therapy at 5 years, use of statins, on-pump coronary artery bypass grafting, multiple arterial grafts, and higher physical component score and mental component score were associated with lower mortality at 10 years. Numerous scores and prediction models were developed to help individualize risk assessment. Machine learning has emerged as a novel approach for developing risk models.</p

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. Result 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

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

The geographical disparity in the pathophysiological pattern of coronary artery disease (CAD) among patients undergoing percutaneous coronary intervention (PCI) is unknown. To elucidate the geographical variance in the pathophysiological characteristics of CAD. 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. 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. 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. [Abstract copyright: Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.

Can Machine Learning Aid the Selection of Percutaneous vs Surgical Revascularization?

Background: In patients with 3-vessel coronary artery disease (CAD) and/or left main CAD, individual risk prediction plays a key role in deciding between percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG). Objectives: The aim of this study was to assess whether these individualized revascularization decisions can be improved by applying machine learning (ML) algorithms and integrating clinical, biological, and anatomical factors. Methods: In the SYNTAX (Synergy between PCI with Taxus and Cardiac Surgery) study, ML algorithms (Lasso regression, gradient boosting) were used to develop a prognostic index for 5-year death, which was combined, in the second stage, with assigned treatment (PCI or CABG) and prespecified effect-modifiers: disease type (3-vessel or left main CAD) and anatomical SYNTAX score. The model's discriminative ability to predict the risk of 5-year death and treatment benefit between PCI and CABG was cross-validated in the SYNTAX trial (n = 1,800) and externally validated in the CREDO-Kyoto (Coronary REvascularization Demonstrating Outcome Study in Kyoto) registry (n = 7,362), and then compared with the original SYNTAX score II 2020 (SSII-2020). Results: The hybrid gradient boosting model performed best for predicting 5-year all-cause death with C-indexes of 0.78 (95% CI: 0.75-0.81) in cross-validation and 0.77 (95% CI: 0.76-0.79) in external validation. The ML models discriminated 5-year mortality better than the SSII-2020 in the external validation cohort and identified heterogeneity in the treatment benefit of CABG vs PCI. Conclusions: An ML-based approach for identifying individuals who benefit from CABG or PCI is feasible and effective. Implementation of this model in health care systems—trained to collect large numbers of parameters—may harmonize decision making globally.</p

The ability of computed tomography angiography to predict 5-year mortality in the SYNTAX III REVOLUTION trial

Background The feasibility of using coronary computed tomography angiography (CCTA) for long-term prediction of vital prognosis post-revascularization remains unknown. Objectives To compare the prognostic value of the SYNTAX score II 2020 (SS-2020) derived from invasive coronary angiography (ICA) or CCTA in patients with three-vessel disease and/or left main coronary artery disease undergoing percutaneous or surgical revascularization. Methods In the SYNTAX III REVOLUTION trial, the probability of death at five years was retrospectively assessed by calculating the SS-2020 using ICA and CCTA. High- and low-risk patients for mortality were categorized according to the median percentages of predicted mortality based on both modalities. The discriminative abilities of the SS-2020 were assessed using Harrell's C statistic. Results The vital status at five years of the 215 patients revascularized percutaneously (64 patients, 29.8%) or surgically (151 patients, 70.2%) was established through national registries. In patients undergoing revascularization, the SS-2020 was possibly helpful in discriminating vital prognosis at 5 years, with similar results seen with ICA and CCTA (C-index with ICA ​= ​0.75, intercept ​= ​−0.19, slope ​= ​0.92 and C-index with CCTA ​= ​0.75, intercept ​= ​−0.22, slope ​= ​0.99). In high- and low-risk patients, Kaplan-Meier estimates showed significant, and almost identical relative differences in observed mortality, irrespective of imaging modality (ICA: 93.8% vs 78.7%, log-lank P ​< ​0.001; CCTA: 93.7% vs 78.5%, log-lank P ​< ​0.001). Conclusions The predictive ability of the SS-2020 for five-year all-cause mortality derived from ICA and CCTA was comparable, and could helpfully discriminate vital prognosis in high- and low-risk patients

Geographic disparity in 10-year mortality after coronary artery revascularization in the SYNTAXES trial

Aims: to investigate geographic disparity in long-term mortality following revascularization in patients with complex coronary artery disease (CAD). Methods and results: the SYNTAXES trial randomized 1800 patients with three-vessel and/or left main CAD to percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) and assessed their survival at 10 years. Patients were stratified according to the region of recruitment: North America (N-A, n = 245), Eastern Europe (E-E, n = 189), Northern Europe (N-E, n = 425), Southern Europe (S-E, n = 263), and Western Europe (W-E, n = 678), which also served as the reference group. Compared to W-E, patients were younger in E-E (62 vs 65 years, p &lt; 0.001), and less frequently male in N-A (65.3% vs 79.6%, p &lt; 0.001). Diabetes (16.0% vs 25.4%, p &lt; 0.001) and peripheral vascular disease (6.8% vs 10.9%, p = 0.025) were less frequent in N-E than W-E. Ejection fraction was highest in W-E (62% vs 56%, p &lt; 0.001). Compared to W-E, the mean anatomic SYNTAX score was higher in S-E (29 vs 31, p = 0.008) and lower in N-A (26, p &lt; 0.001). Crude ten-year mortality was similar in N-A (31.6%), and W-E (30.7%), and significantly lower in E-E (22.5%, p = 0.041), N-E (21.9%, p = 0.003) and S-E (22.0%, p = 0.014). Compared to W-E, adjusted mortality in N-E (HR 0.85, p = 0.019) and S-E (HR 0.72, p = 0.043) remain significantly lower after adjustment for pre- and peri-procedural factors, but no significant interaction (P interaction = 0.728) between region and modality of revascularization was seen. Conclusion: in the era of globalization, knowledge, and understanding of geographic disparity are of paramount importance for the correct interpretation of global studies. </p