Left Main Revascularization Research Articles

Fallacies and Possible Remedies of the SYNTAX Score.

Quite a few studies have revealed the clinical values regarding the outcome predictions in the cohort of the Synergy between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery (SYNTAX) trial and decision-making with the SYNTAX score. The Evaluation of Xience Everolimus-Eluting Stent Versus Coronary Artery Bypass Surgery for Effectiveness of Left-Main Revascularization (EXCEL) and Nordic-Baltic-British left main revascularization (NOBLE) studies are the largest international randomized studies so far, comparing percutaneous coronary intervention (PCI) and coronary artery bypass graft (CABG) in the treatment of left main coronary artery disease. Unfortunately, both studies failed to validate the value of the SYNTAX score in the selection of revascularization strategies for patients with coronary artery diseases (CAD).. This scenario prompted us to reconsider the inherent fallacies of the SYNTAX score in its derivation. We pointed out eight fallacies for the SYNTAX score in this paper. A recently developed Coronary Artery Tree description and Lesion EvaluaTion (CatLet) score, available at http://www.catletscore.com, a novel angiographic scoring system, could be the remedies for the SYNTAX score.

Abstract 14575: Systematic Review and Meta-analysis of Intravascular Ultrasound-guided Percutaneous Left-main Coronary Artery Intervention

Introduction: Previous meta-analyses have reported reduced cardiovascular mortality and myocardial infarction in intravascular ultrasound-guided (IVUS) stent implantation in comparison to angiography-only approach. However, these studies have unanimously excluded patients with unprotected left-main coronary artery (LMCA) disease, questioning its widespread applicability. We performed a systematic review and meta-analysis to investigate the prognostic significance of IVUS-guided LMCA intervention. Methods: Studies comparing clinical outcomes between IVUS-guided and angiography-only percutaneous LMCA intervention were identified through PubMed, Cochrane and EMBASE databases until June, 2020. Data was analyzed using a random effect model to calculate the relative odds of all-cause death, cardiac death, left-main revascularization, myocardial infarction, stent thrombosis and stroke. Results: A total of 13 studies comprising 7680 patients were included. The odds of all-cause death (OR 0.6, 95%CI 0.47-0.78; p<0.0001), cardiac death (OR 0.37, 95%CI 0.26-0.54; p<0.00001), left-main revascularization (OR 0.63, 95%CI 0.45-0.89; p=0.009) and myocardial infarction (OR 0.77 [95%CI 0.60-0.98; p=0.04]) were significantly lower in patients who underwent IVUS-guided LMCA stent implantation compared to angiography-only approach. There was no significant difference observed in the relative odds of stent thrombosis (OR 0.57, 95%CI 0.31-1.05; p=0.07) and stroke (OR 1.7, 95%CI 0.56-5.14; p=0.35) between the two arms at least 1-year of the index procedure. A subgroup analysis based on study design and sensitivity analysis based on the characteristics of the included studies mirrored the pooled results. Conclusion: IVUS-guided LMCA intervention is associated with overall improved cardiovascular outcomes than angiography-only approach. Large scale randomized controlled trials are needed to validate our findings.

Angiographic SYNTAX score reduction in de novo left main coronary stenosis patients over the last decade: implications for revascularization approach

Abstract Introduction Percutaneous management of left main (LM) coronary artery stenosis is an acceptable alternative to surgery in selected group of patients. Purpose To investigate potential angiographic trends in de novo LM coronary artery stenosis patients. Those may impact revascularization mode but remain undetermined. Methods Clinical records and all consecutive coronary angiograms in our Institution from 1st January 2010 to 31stDecember 2019 were evaluated to identify those with newly diagnosed angiography-significant (≥50% lumen diameter reduction) LM stenosis. Angiographic SYNTAX score (SS) assessment was performed by agreement of two experienced analysts (an angiographic core lab analyst and a Heart Team interventional cardiologist) on anonymized angiograms. Values of the overall SS, SS of the LM lesion and SS beyond LM were determined according to SS assessment methodology. Pearson's correlation and Fisher transformation were used to evaluate parametric variables. Spearman's rho was used to determine trends. Results Overall, out of 12315 coronary angiographies performed in de novo referrals in the last decade, 357 (2.90%) showed significant left main stenosis; the proportion varied from 2.30% to 3.48% annually. Patient mean age was 68.8 years (23.3% women). No temporal trends in patient age or gender occurred over the last decade while the overall SS deceased from a mean value of 35 to 28 (SC=−0.16, p=0.003). Further analysis showed a particular negative trend in the non-LM-SS (SC=−0.17, p=0.001) but not in the LM-SS (SC=0.04, p=0.47). No temporal trend was present is the prevalence of isolated LM stenosis (p=0.48) and no temporal trend in the LM stenosis angiographic severity (<70% vs. ≥70%; p=0.61), LM stenosis location (ostial/mid/bifurcation/entire left main; p=0.30) nor in the number of LM segments affected (SC=0.05, p=0.30). Reduction in the non-LM-SS was associated with a decrease in the number of coronary arteries with a significant angiographic atherosclerotic involvement (SC=−0.12, p=0.03) and in the number of coexisting total occlusions (SC=−0.25, p<0.001). Conclusion(s) (1) In patients with newly diagnosed LM critical stenosis overall angiographic SS showed a statistically significant negative trend over last decade, with a reduction from mean 35 (2010) to 28 points (2019); a finding that may be related to a change in the angiographic presentation of the disease or an earlier identification of LM stenosis patients over time. (2) The overall SS reduction was driven by a decrease in non-LM-SS. This, taken together with the overall SS reduction from above 32 to below 32, favours (as per current guidelines) the endovascular approach to left main revascularization. Our findings suggest an increase in the proportion of LM stenosis patients with angiography feasible to percutaneous intervention. SYNTAX score trends over the last decade Funding Acknowledgement Type of funding source: None

Long-Term Prognostic Impact of Restenosis of the Unprotected Left Main Coronary Artery Requiring Repeat Revascularization.

The aim of this study was to evaluate the prognostic impact of target lesion revascularization (TLR) of the unprotected left main coronary artery (ULMCA) after stent failure. Although drug-eluting stents are safe and effective for treatment of the ULMCA, increased rates of repeat revascularization have been observed. This is a patient-level pooled analysis of the randomized ISAR-LEFT-MAIN (Drug-Eluting-Stents for Unprotected Left Main Stem Disease) and ISAR-LEFT-MAIN-2 (Drug-Eluting Stents to Treat Unprotected Coronary Left Main Disease) trials, in which patients underwent stenting of the ULMCA. The present analysis includes patients who underwent angiography during follow-up. Patients with TLR were compared with those without. Additional long-term clinical follow-up after TLR was conducted, and its influence on mortality was evaluated. Mortality was calculated using the Kaplan-Meier method. Predictors of mortality were assessed in a multivariate analysis. A total of 1,001 patients were eligible, of whom 166 experienced TLR. The 5-year mortality rate was 30.2% in patients with TLR compared with 17.3% in those without TLR (p<0.001). In the multivariate analysis, glomerular filtration rate (-30ml/min; hazard ratio [HR]: 2.25; 95% confidence interval [CI]: 1.54 to 3.27; p<0.001), chronic obstructive pulmonary disease (HR: 4.95; 95%CI: 1.33 to 18.42; p=0.02), and body mass index (+5kg/m2; HR: 1.61; 95%CI: 1.12 to 2.32; p=0.01) were independent predictors of mortality after TLR due to left main stent failure. The type of repeat revascularization and the underlying stent did not influence the mortality after TLR of the ULMCA. Mortality after TLR for left main stent failure is high. Patient-related factors seem to have a greaterimpact on mortality after TLR than other variables.

Implications of Alternative Definitions of Peri-Procedural Myocardial Infarction After Coronary Revascularization

BackgroundVarying definitions of procedural myocardial infarction (PMI) are in widespread use. ObjectivesThis study sought to determine the rates and clinical relevance of PMI using different definitions in patients with left main coronary artery disease randomized to percutaneous coronary intervention (PCI) versus coronary artery bypass grafting (CABG) surgery in the EXCEL (Evaluation of XIENCE versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization) trial. MethodsThe pre-specified protocol definition of PMI (PMIProt) required a large elevation of creatine kinase-MB (CK-MB), with identical threshold for both procedures. The Third Universal Definition of MI (types 4a and 5) (PMIUD) required lesser biomarker elevations but with supporting evidence of myocardial ischemia, different after PCI and CABG. For the PMIUD, troponins were used preferentially (available in 49.5% of patients), CK-MB otherwise. The multivariable relationship between each PMI type and 5-year mortality was determined. ResultsPMIProt occurred in 34 of 935 (3.6%) patients after PCI and 56 of 923 (6.1%) patients after CABG (difference −2.4%; 95% confidence interval [CI]: −4.4% to −0.5%; p = 0.015). The corresponding rates of PMIUD were 37 (4.0%) and 20 (2.2%), respectively (difference 1.8%; 95% CI: 0.2% to 3.4%; p = 0.025). Both PMIProt and PMIUD were associated with 5-year cardiovascular mortality (adjusted hazard ratio [HR]: 2.18 [95% CI: 1.13 to 4.23] and 2.87 [95% CI: 1.44 to 5.73], respectively). PMIProt was associated with a consistent hazard of cardiovascular mortality after both PCI and CABG (pinteraction = 0.86). Conversely, PMIUD was strongly associated with cardiovascular mortality after CABG (adjusted HR: 11.94; 95% CI: 4.84 to 29.47) but not after PCI (adjusted HR: 1.14; 95% CI: 0.35 to 3.67) (pinteraction = 0.004). Results were similar for all-cause mortality and with varying PMIUD biomarker definitions. Only large biomarker elevations (CK-MB ≥10× upper reference limit and troponin ≥70× upper reference limit) were associated with mortality. ConclusionsThe rates of PMI after PCI and CABG vary greatly with different definitions. In the EXCEL trial, the pre-specified PMIProt was associated with similar hazard after PCI and CABG, whereas PMIUD was strongly associated with mortality after CABG but not after PCI. (EXCEL Clinical Trial [EXCEL]; NCT01205776)

Impact of Peri-Procedural Myocardial Infarction on Outcomes After Revascularization

BackgroundNumerous definitions for peri-procedural myocardial infarction (PMI) following percutaneous coronary intervention (PCI) and coronary bypass grafting (CABG) surgery exist. ObjectivesThe purpose of this study was to investigate the PMI rates according to various definitions, their clinically relevant association with all-cause mortality at 10 years, and their impact on composite endpoints at 5 years in the SYNTAXES (Synergy between PCI with Taxus and Cardiac Surgery Extended Survival) trial. MethodsPMI was classified as a myocardial infarction occurring within 48 h of the procedure according to definitions of the SYNTAX (TAXUS Drug-Eluting Stent Versus Coronary Artery Bypass Surgery for the Treatment of Narrowed Arteries), ISCHEMIA (International Study Of Comparative Health Effectiveness With Medical And Invasive Approaches), and EXCEL (Evaluation of XIENCE versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization) trials; the Fourth Universal Definition of MI; and the Society for Cardiovascular Angiography and Interventions (SCAI). Of the 1,800 patients enrolled, 1,652 with creatine kinase and/or creatine kinase-myocardial band (CK-MB) post-procedure were included. The association between PMI and mortality was analyzed by Cox regression. ResultsPMI rates according to the SYNTAX and Fourth Universal Definition of MI, both of which required CK-MB elevation and electrocardiographic evidence of permanent myocardial damage, were 2.7% and 3.0%, respectively, in the PCI arm versus 2.4% and 2.1%, respectively, in the CABG arm. PMI rates according to the SCAI or EXCEL definition were higher in the PCI (5.7%) and CABG (16.5%) arms. PMIs according to the SYNTAX and Fourth Universal Definition of MI were more strongly associated with mortality than EXCEL and SCAI PMIs defined by isolated enzyme elevation when CK-MB was more than 10 times ULN. The impact of these “enzyme-driven events” on time-to-event curves and the composite endpoints was greater in the surgical cohort. PMIs after PCI were associated with 10-year mortality regardless of definition, whereas their impact on mortality after CABG was limited to 1 year. ConclusionsThe rates of PMI are highly dependent on their definition, which affects time-to-event curves, composite endpoints, and their lethal prognostic relevance. (Synergy Between PCI With TAXUS and Cardiac Surgery: SYNTAX Extended Survival [SYNTAXES]; NCT03417050; SYNTAX Study: TAXUS Drug-Eluting Stent Versus Coronary Artery Bypass Surgery for the Treatment of Narrowed Arteries [SYNTAX]; NCT00114972)

NOBLE trial-is it time to revise the guidelines?

The Nordic-Baltic-British left main revascularization trial (NOBLE) is a prospective, randomized, multicentre, non-inferiority trial comparing percutaneous coronary angioplasty (PCI) with coronary artery bypass grafting (CABG) for revascularization of patients with unprotected left main coronary artery (LMCA) stenosis. The primary outcome was a combined endpoint of all-cause mortality, stroke, non-procedural myocardial infarction and repeat revascularization. CABG was found to be superior to PCI with respect to the 5-year MACCE rates (28% vs. 19%) with a hazard ratio (HR) of 1.58 (95% CI 1.24-2.01). All-cause mortality rates were similar, but PCI was associated with increased occurrence of non-procedural myocardial infarction (p = 0.0002) and repeat revascularization (p = 0.0009). There was no difference in the stroke rates (p = 0.11) at 5years. Currently, European Society of Cardiology and the European Association for Cardio-Thoracic Surgery (ESC/EACTS) guidelines on myocardial revascularization assign a class 1A recommendation to PCI in patients with unprotected LMCA stenosis with a SYNTAX score < 23. The findings of the NOBLE trial challenge this premise.

Bayesian Interpretation of the EXCEL Trial and Other Randomized Clinical Trials of Left Main Coronary Artery Revascularization

Patients with left main coronary artery disease have improved outcomes with coronary revascularization compared with medical therapy, but the choice of optimal revascularization technique is unresolved. To use bayesian methods to analyze the risk differences for patients with left main coronary artery disease randomized to treatment with coronary artery bypass surgery (CABG) compared with those randomized to percutaneous coronary intervention (PCI) in recent randomized clinical trials (RCTs). A systematic review using the PubMed database with the query string "(left main disease) and (PCI or CABG) and (5-year follow-up) and (clinical trial)" identified all RCTs from January 1996 to January 2020 comparing CABG to PCI for treatment of patients with left main coronary artery disease and with 5-year follow-up data. With the use of bayesian methods, the largest and most publicized RCT (EXCEL; Evaluation of XIENCE Versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization; 2019) was reanalyzed (1) as an isolated entity using noninformative priors and (2) in the context of previous knowledge using informative priors derived from similar trials. Published aggregate data were used with assignments from each trial following the original intention-to-treat principle. Combining EXCEL data with varying levels of prior information using Bayes theorem provided final (posterior) probability distributions for primary and secondary outcomes. A composite end point of death, nonfatal myocardial infarction, and stroke was the primary EXCEL outcome and was accordingly the primary outcome for this reanalysis. Secondary analyses were performed for isolated all-cause mortality and for the composite outcome along with repeated revascularization procedures. When EXCEL data were analyzed using the originally stated noninferiority design, the 5-year primary outcome difference reported (2.8%; 95% CI, -0.9% to 6.5%) exceeded the predefined 4.2% noninferiority margin; thus, the null hypothesis of PCI inferiority could not be rejected. By contrast, the present bayesian analysis of the EXCEL primary outcome estimated 95% probability that the 5-year primary outcome difference was increased with PCI compared with CABG and 87% probability that this difference was greater than 1 extra event per 100 patients treated. Bayesian analyses also suggested 99% probability that EXCEL total mortality was increased with PCI and 94% probability that this absolute difference exceeded 1 extra deaths per 100 treated. A systematic review identified 3 other RCTs that studied the same question. The incorporation of this prior knowledge reduced the estimated probability of any excess mortality with PCI to 85%. For the secondary composite end point, which also included repeated revascularizations, there were estimated probabilities of 98% for at least 4 extra events and of 90% for at least 5 extra events per 100 patients treated with PCI. Bayesian analysis assisted in RCT data interpretation and specifically suggested, whether based on EXCEL results alone or on the totality of available evidence, that PCI was associated with inferior long-term results for all events, including mortality, compared with CABG for patients with left main coronary artery disease.

One- and 3-year outcomes of percutaneous bifurcation left main revascularization with modern drug-eluting stents: a systematic review and meta-analysis.

Optimal percutaneous coronary intervention (PCI) strategy for coronary left main (LM) bifurcation lesions remains controversial. We performed systematic review and meta-analysis comparing one and 3-year clinical outcomes of 1- and 2- stent strategies using modern drug eluting stents (DESs) for revascularization of LM bifurcation disease. We systematically identified all investigations published between January 2015 and February 2020 comparing the use of single versus double-stent strategies for the revascularization of LM bifurcation lesions. The primary endpoint was 1- and 3-years all-cause mortality. Secondary outcomes included target lesion revascularization (TLR), target lesion failure (TLF), major adverse cardiovascular vents (MACEs) and cardiovascular (CV) mortality while the tertiary outcome was overall occurrence of stent thrombosis (ST) at 1- and 3-years. No significant differences were observed between the two groups in terms of all-cause mortality rate both at 1 and 3-year follow-up. Single stent strategy was associated with a significantly lower risk of TLR (OR 0.78, 95% CI 0.62- 0.97, p = 0.03, I2 = 61%) as well as of MACEs (OR 0.78, 95% CI 0.63-0.97, I2 = 24%) compared to 2-stent strategy. Conversely no significant differences between the two groups were observed in terms of TLF, CV mortality and ST during the same follow-up period. In patients with LM bifurcation disease, single stent strategy demonstrated lower rate of MACEs and TLR but was not superior to 2-stent strategy in terms of CV mortality, TLF and ST at 1 and 3-year follow-up.

May 2020 at a glance: ischaemic heart failure and sex-related differences.

Almost half of patients with heart failure (HF) had an ischaemic aetiology.1 However, HF occurrence in patients with chronic coronary syndrome is unclear. During a 5-year follow-up, Parma et al.2 observed a 16.4% incidence of cardiovascular death, HF hospitalization and new-onset HF (primary endpoint) in patients with chronic coronary syndrome without history of HF. Hospitalization for HF and new-onset HF occurred in 2.8% and 11.6% of patients, respectively. Malik et al.3 showed that the risk of developing HF at 5 years after the diagnosis of diabetes is low in patients without ischaemic heart disease (IHD) or end-stage renal disease (ESRD) (4%), intermediate (8-12%) in diabetic subjects with IHD or ESRD, and high (20%) in those with diabetes complicated by both IHD and ESRD. Sama et al.4 performed a network analysis to recognize pathophysiological pathways distinguishing ischaemic from non-ischaemic HF. They identified six pathways, related to inflammation, endothelial dysfunction superoxide production, coagulation, and atherosclerosis, and five key network proteins, acid phosphatase 5, epidermal growth factor receptor, insulin-like growth factor binding protein-1, plasminogen activator urokinase receptor, and secreted phosphoprotein 1, as specific for ischaemic HF and potential targets for specific treatment. The role of coronary revascularization in asymptomatic patients with HF of ischaemic aetiology remains debated.5 A comprehensive review showing the pathophysiology and diagnosis of this condition, as well as the role of coronary revascularization, is reported in this issue.6 Thuijs et al.7 performed a pre-specified analysis from the Evaluation of XIENCE Versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization (EXCEL) trial. They found no differences in the composite of death, stroke, or myocardial infarction at 3 years in patients stratified by left ventricular ejection fraction (LVEF) and treated by percutaneous vs. surgical revascularization of the left main coronary artery. However, patients with reduced LVEF had worse outcomes compared to the others. Whether indications for implantable cardioverter-defibrillator (ICD) therapy after acute myocardial infarction should be merely based on LVEF is debated.8 Docherty et al.9 developed and validated a risk model to predict the occurrence of sudden cardiac death early and up to 2 years after myocardial infarction. Including simple variables, this score could easily identify patients who may benefit from ICD therapy. Fudim et al.10 noted that 1-year mortality after ICD implantation, for primary or secondary prevention, increased with increasing age reaching an incidence of 32% in the oldest patients (median age 82 years). This confirms the importance of a careful selection of ICD candidates in order to avoid futility. Treatment of ischaemic HF with mesenchymal stem cells is an area of active research.11 Mathiesen et al.11 reported the long-term results of the Autologous Mesenchymal Stromal Cell Therapy in Heart Failure (MCS-HF) trial, a 2:1 randomized double-blind trial comparing intramyocardial injections of autologous mesenchymal stromal cells (MSCs) vs. placebo in patients with ischaemic HF. They found a significant reduction in left ventricular end-systolic volume in the treatment compared to the placebo arm. Also LVEF, stroke volume and myocardial mass improved after MCS injection. Studies exploring the efficacy of heterologous MCSs in ischaemic HF are ongoing.12 Sex-related differences in HF biomarkers are known.13 Suthahar et al.14 reviewed sex-specific differences and the interaction with obesity. Rossello et al.15 conducted a patient-level meta-analysis including three randomized trials comparing the effect of mineralocorticoid receptor antagonists (MRA) and placebo. Women differ from men in their clinical features and event rates. However, no sex-specific impact of MRA on cardiovascular mortality and HF hospitalization was noted. Interestingly, sex, and namely male sex, was an independent predictor of MRA non-use in a recent large survey.16

Outcomes After Left Main Coronary Artery Revascularization by Percutaneous Coronary Intervention or Coronary Artery Bypass Grafting According to Smoking Status

Cigarette smoking is a well-known risk factor for coronary artery disease (CAD). However, the impact of smoking on outcomes after coronary revascularization, especially in patients with left main CAD (LMCAD) is less well understood. The EXCEL trial randomized 1,905 patients with LMCAD and visually assessed low or intermediate anatomical complexity (SYNTAX score ≤32) to PCI with everolimus-eluting stents or CABG. Patients were categorized according to smoking status (current, former, or never), and their outcomes at 5 years were compared by logistic regression with follow-up time included as a log-transformed offset variable. The primary endpoint was a composite of death, myocardial infarction, or stroke. Among 1893 patients with known smoking status at baseline, 416 (22%) were current smokers and 774 (41%) were former smokers. The crude rates of the primary endpoint were 19.5% for never smokers, 20.5% for former smokers (p = 0.61 vs never smokers), and 23.1% for smokers (p = 0.15 vs never smokers). Compared with never smokers, the adjusted risk of the primary endpoint was higher for current smokers (adjOR 1.82, 95% confidence interval [CI] 1.126 to 2.63; p = 0.001), but not for former smokers (adjOR 1.00, 95% CI 0.75 to 1.33, p = 0.10). The relative efficacy of PCI versus CABG for the 5-year primary endpoint was similar irrespective of smoking status (Pinteraction = 0.22). In conclusion, current smokers in the EXCEL trial had a higher adjusted 5-year risk of the primary composite endpoint of death, myocardial infarction, or stroke than never smokers, whereas former smokers were not at increased risk. Active smoking was a risk factor after LMCAD revascularization irrespective of revascularization method.

First left main coronary revascularization with adjuvant intracoronary lithotripsy in Spain

First left main coronary revascularization with adjuvant intracoronary lithotripsy in Spain

Impact of left ventricular ejection fraction on clinical outcomes after left main coronary artery revascularization: results from the randomized EXCEL trial.

To evaluate the impact of left ventricular ejection fraction (LVEF) on 3-year outcomes in patients with left main coronary artery disease (LMCAD) undergoing percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) in the EXCEL trial. The EXCEL trial randomized patients with LMCAD to PCI with everolimus-eluting stents (n=948) or CABG (n=957). Among 1804 patients with known baseline LVEF, 74 (4.1%) had LVEF <40% [heart failure with reduced ejection fraction (HFrEF)], 152 (8.4%) LVEF 40-49% [heart failure with mid-range ejection fraction (HFmrEF)] and 1578 (87.5%) LVEF ≥50% (heart failure with preserved ejection fraction). Patients with HFrEF vs. HFmrEF vs. preserved LVEF experienced a longer postoperative hospital stay (9.0 vs. 7.0 vs. 6.0 days, P=0.02) with greater peri-procedural complications after CABG, while hospital stay after PCI was unaffected by LVEF (1.5 vs. 2.0 vs. 1.0 days, P=0.20). The composite primary endpoint of death, stroke, or myocardial infarction at 3 years was 29.3% (PCI) vs. 27.6% (CABG) in patients with HFrEF, 16.2% vs. 15.0% in patients with HFmrEF, and 14.5% vs. 14.6% in those with preserved LVEF, respectively (Pinteraction =0.90). Smoothing spline analysis demonstrated that the 3-year risk of all-cause death increased when LVEF decreased, both in patients undergoing CABG and PCI. In the EXCEL trial, the composite rate of death, stroke or myocardial infarction at 3 years was significantly higher in patients with HFrEF compared with HFmrEF or preserved LVEF, driven by an increased rate of all-cause death. No significant differences after PCI vs. CABG were observed among patients with HFrEF, HFmrEF and preserved LVEF. Longer-term follow-up could provide important insights on differences in clinical outcomes that might emerge over time. ClinicalTrials.gov Identifier NCT01205776.

Rates and Independent Correlates of 10-Year Major Adverse Events and Mortality in Patients Undergoing Left Main Coronary Arterial Revascularization

Patients who underwent myocardial revascularization for significant left main coronary artery disease (LMCA) are at high risks of ischemic events and death during follow-up. We sought to determine the independent correlates for very long-term outcomes after LMCA revascularization, which would be clinical value for risk stratification in such high-risk patients. The 10-year rates of clinical outcomes and independent correlates of adverse events were evaluated in 2,240 patients with LMCA disease in the MAIN-COMPARE registry, including 1,102 patients who underwent stenting and 1,138 who underwent coronary artery bypass grafting. The primary outcome was the composite of all-cause death, Q-wave myocardial infarction, or stroke. Secondary outcomes were all-cause mortality and target-vessel revascularization (TVR). The 10-year rates of the primary composite outcome, all-cause mortality, and TVR were 24.7%, 22.2%, and 13.6%, respectively. Age >65 years, diabetes, previous heart failure, cerebrovascular disease, peripheral arterial disease, chronic renal failure, atrial fibrillation, ejection fraction <40%, and distal LMCA bifurcation disease were independent correlates of the primary outcome in the overall population. Several clinical and anatomic parameters were also identified as independent correlates of all-cause death and TVR. Interaction analysis showed no heterogeneities of the effects of variables depending on revascularization type. These clinical descriptors can assist clinicians in identifying high-risk patients within the broad range of risk for patients who underwent LMCA revascularization.

Mortality After Repeat Revascularization Following PCI or CABG for Left Main Disease: The EXCEL Trial

ObjectivesThe aim of this study was to investigate the incidence and impact on mortality of repeat revascularization after index percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) for left main coronary artery disease (LMCAD). BackgroundThe impact on mortality of the need of repeat revascularization following PCI or CABG in patients with unprotected LMCAD is unknown. MethodsAll patients with LMCAD and site-assessed low or intermediate SYNTAX (Synergy Between PCI With Taxus and Cardiac Surgery) scores randomized to PCI (n = 948) or CABG (n = 957) in the EXCEL (Evaluation of XIENCE Versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization) trial were included. Repeat revascularization events were adjudicated by an independent clinical events committee. The effect of repeat revascularization on mortality through 3-year follow-up was examined in time-varying Cox regression models. ResultsDuring 3-year follow-up, there were 346 repeat revascularization procedures among 185 patients. PCI was associated with higher rates of any repeat revascularization (12.9% vs. 7.6%; hazard ratio: 1.73; 95% confidence interval: 1.28 to 2.33; p = 0.0003). Need for repeat revascularization was independently associated with increased risk for 3-year all-cause mortality (adjusted hazard ratio: 2.05; 95% confidence interval: 1.13 to 3.70; p = 0.02) and cardiovascular mortality (adjusted hazard ratio: 4.22; 95% confidence interval: 2.10 to 8.48; p < 0.0001) consistently after both PCI and CABG (pint = 0.85 for both endpoints). Although target vessel revascularization and target lesion revascularization were both associated with an increased risk for mortality, target vessel non–target lesion revascularization and non–target vessel revascularization were not. ConclusionsIn the EXCEL trial, repeat revascularization during follow-up was performed less frequently after CABG than PCI and was associated with increased mortality after both procedures. Reducing the need for repeat revascularization may further improve long-term survival after percutaneous or surgical treatment of LMCAD. (EXCEL Clinical Trial; NCT01205776)

Off-pump versus on-pump bypass surgery for left main coronary artery disease (EXCEL study) - is experience the unknown variable?

A post hoc analysis of the Evaluation of XIENCE versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization (EXCEL) data compared off-pump coronary artery bypass (OPCAB) technique with conventional coronary artery bypass grafting (CABG). It was reported that OPCAB was associated with lower rate of revascularization especially in the inferolateral wall and carried increased risk of 3-year all-cause mortality compared to on-pump CABG. However, the study does not provide any information on the experience of participating surgeons which is a key determinant of outcomes in OPCAB surgery. In the absence of this key variable, the extrapolation and applicability of this finding to the wider surgical practice, especially in countries like India and Japan, may not be accurate.

The impact of coronary artery disease severity on long-term outcomes in unprotected left main coronary artery revascularization.

The optimal treatment modality for left main coronary artery (LMCA) disease is still controversial. The aim of this study was to investigate long-term prognostic determinants of percutaneous coronary intervention (PCI) for LMCA disease and the role of coronary artery disease (CAD) severity in this population. A total of 60 consecutive patients who underwent LMCA PCI were enrolled in this study. Baseline demographic and clinical variables were recorded, as well as the SYNTAX score (SS), SS II, and residual SS (rSS). The primary endpoints of the study were all-cause death, non procedural myocardial infarction (MI), and stroke. The patients were then divided into 2 groups: patients without a composite endpoint (Group 1) and those with a composite endpoint (Group 2). Of the 60 patients, 15 (25%) were female and the mean age was 59.8±14.7 years. The median follow-up time was 25 months (range: 12-33 months). A primary composite endpoint was observed in 16 patients (26.7%): mortality occurred in 10 patients (16.7%), 4 (6.6%) experienced MI, and stroke was seen in 2 patients (3.3%). Target vessel revascularization was performed in 3 patients (5%). The mean SYNTAX score (Group 1: 19.9±9.8; Group 2: 26.8±12.2; p=0.029), SS II PCI (Group 1: 27.7 [range: 17.7-36.8]; Group 2: 34.2 [range: 27.9-55.2]; p=0.030) and rSS (Group 1: 0 [range: 0-5]; Group 2: 12.5 [range: 3.5-22.5]; p=0.001) were higher in patients with a composite endpoint. Additionally, creatinine (odds ratio [OR]: 13.098; 95% confidence interval [CI]: 1.471-116.620; p=0.021), non-postdilatation (OR: 8.340; 95% CI: 1.230-56.570; p=0.030), and rSS (OR: 1.157; 95% CI: 1.024-1.307; p=0.019) were independent predictors of a primary composite endpoint. CAD severity has prognostic value for mortality, MI, and stroke in patients who undergo unprotected LMCA PCI. An increased initial SS and post-procedural rSS were related to adverse cardiovascular outcomes. The rSS was also an independent predictor of major adverse cardiac and cerebrovascular events and mortality.

Impact of non-respect of SYNTAX score II recommendation for surgery in patients with left main coronary artery disease treated by percutaneous coronary intervention: an EXCEL substudy.

The SYNTAX score II (SSII) was developed from the SYNTAX trial to predict the 4-year all-cause mortality after left main or multivessel disease revascularization and to facilitate the decision-making process. The SSII provides the following treatment recommendations: (i) coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI) (equipoise risk), (ii) CABG preferred (excessive risk for PCI) or (iii) PCI preferred (excessive risk for CABG). We sought to externally validate SSII and to investigate the impact of not abiding by the SSII recommendations in the randomized EXCEL trial of PCI versus CABG for left main disease. The calibration plot of predicted versus observed 4-year mortality was constructed from individual values of SSII in EXCEL. To assess overestimation versus underestimation of predicted mortality risk, an optimal fit regression line with slope and intercept was determined. Prospective treatment recommendations based on SSII were compared with actual treatments and all-cause mortality at 4 years. SSII variables were available from EXCEL trial in 1807/1905 (95%) patients. For the entire cohort, discrimination was possibly helpful (C statistic = 0.670). SSII-predicted all-cause mortality at 4 years overestimated the observed mortality, particularly in the highest-risk percentiles, as confirmed by the fit regression line [intercept 2.37 (1.51-3.24), P = 0.003; slope 0.67 (0.61-0.74), P < 0.001]. When the SSII-recommended treatment was CABG, randomized EXCEL patients treated with PCI had a trend towards higher mortality compared with those treated with CABG (14.1% vs 5.3%, P = 0.07) in the as-treat population. In the intention-to-treat population, patients randomized to PCI had higher mortality compared with those randomized to CABG (15.1% vs 4.1%, P = 0.02), when SSII recommended CABG. In the EXCEL trial of patients with left main disease, the SSII-predicted 4-year mortality overestimated the 4-year observed mortality with a possibly helpful discrimination. Non-compliance with SSII CABG treatment recommendations (i.e. randomized to PCI) was associated with higher 4-year all-cause mortality.

P3128Unprotected left main revascularization in patients with acute myocardial infarction: insights of a multicenter national registry

Abstract Introduction Unlike stable coronary disease, there is no consensus about the best revascularization strategy for unprotected left main coronary artery (ULMCA) disease associated with acute myocardial infarction (MI). Recent studies have shown that percutaneous coronary intervention (PCI) is technically feasible with acceptable outcomes, making it a reasonable alternative to surgical revascularization (CABG). Aims To describe the practice of ULMCA revascularization in MI patients (pts) and its evolution over an 9-year period. To analyze the prognosis of this population and determine the effect of revascularization on outcome. Methods Retrospective, multicenter national observational study that included 19 430 MI pts from October 2010 to December 2018. Pts who presented ULMCA as culprit lesion were selected and then compared the subgroup that underwent revascularization by PCI alone versus (vs.) CABG alone. Primary endpoint (PE) was a composite of all-cause death, nonfatal re-MI and nonfatal stroke during hospital stay. Secondary endpoint (SE) was all-cause death rate at 1-year after hospital discharge. Results 204 pts with ULMCA as culprit lesion were selected (1.1% of all pts): 77.9% male, mean age 69±12 years, 97 (47.5%) underwent CABG alone, 92 (45.1%) PCI alone, 10 (4.9%) no revascularization and 5 (2.5%) both strategies. At admission, pts undergoing PCI alone presented more frequently with ST-segment elevation, persistent chest pain, cardiogenic shock and higher values of GRACE risk score. During hospital stay, severe left ventricular (LV) systolic dysfunction (&lt;30%), need for mechanical ventilation, sustained ventricular tachycardia and aborted cardiac sudden death were also more common in these pts. Concerning PE, global rate was 18.5% (27 deaths, 6 nonfatal re-MI and 2 nonfatal stroke). It was significantly higher in pts undergoing PCI alone (32.6% vs. 3.1%, p&lt;0.01). After adjustment, surgical revascularization had 98% lower odds of PE occurrence compared to PCI (OR 0.02, 95% CI 0.002–0.22, p&lt;0.01). Cardiogenic shock at admission (OR 5.06, 95% CI 1.21–21.11, p=0.03) and severe LV systolic dysfunction (OR 7.77, 95% CI 1.49–40.56, p=0.02) were also independent predictors of adverse outcome. One-year all-cause death rate was 4.9%, with no significant difference at survival curves between PCI vs. CABG (Log-Rank p=0.96).Over the 9-year, there was not a significant change in the use of one revascularization technique over the other. Conclusions MI with ULMCA as culprit lesion is infrequent and associated with a high rate of adverse events during hospital stay. PCI was preferred in higher risk pts but, even after adjustment, it was associated with a less favorable short-term outcome compared to surgical strategy. Nevertheless, long-term prognosis was excellent in hospital survivors with no difference between both techniques. Randomized trials are needed to determine the ideal revascularization strategy for these pts.

TCT-308 Impact of Periprocedural Major Adverse Events After PCI and CABG on Long-Term Outcomes in Patients With Left Main Disease: The EXCEL Trial

In the EXCEL trial, periprocedural major adverse events (MAE) were more frequent after coronary artery bypass graft (CABG) versus percutaneous coronary intervention (PCI) for treatment of left main (LM) disease. The association between composite and individual MAE after LM revascularization and long