Percutaneous ventricular assist device for higher-risk percutaneous coronary intervention in surgically ineligible patients: Indications and outcomes from the OPTIMUM study.

BACKGROUND: Indications and outcomes for percutaneous ventricular assist device (pVAD) use in surgically ineligible patients undergoing percutaneous coronary intervention (PCI) remain poorly characterized. AIMS: We sought to describe the use and timing of pVAD and outcome in surgically ineligible patients. METHODS: Among 726 patients enrolled in the prospective OPTIMUM study, clinical and health status outcomes were assessed in patients who underwent pVAD-assisted PCI and those without pVAD. RESULTS: Compared with patients not receiving pVAD (N = 579), those treated with pVAD (N = 142) more likely had heart failure, lower left ventricular ejection fraction (30.7 ± 13.6 vs. 45.9 ± 15.5, p < 0.01), and higher STS 30-day predicted mortality (4.2 [2.1-8.0] vs. 3.3 [1.7-6.6], p = 0.01) and SYNTAX scores (36.1 ± 12.2, vs. 31.5 ± 12.1, p < 0.01). While the pVAD group had higher in-hospital (5.6% vs. 2.2%, p = 0.046), 30-day (9.0% vs. 4.0%, p = 0.01) and 6-month (20.4% vs. 11.7%, p < 0.01) mortality compared to patients without pVAD, this difference appeared to be largely driven by significantly higher mortality among the 20 (14%) patients with unplanned pVAD use (30% in-hospital mortality with unplanned PVAD vs. 1.6% with planned, p < 0.01; 30-day mortality, 38.1% vs. 4.5%, p < 0.01). The degree of 6-month health status improvement among survivors was similar between groups. CONCLUSION: Surgically ineligible patients with pVAD-assisted PCI had more complex baseline characteristics compared with those without pVAD. Higher mortality in the pVAD group appeared to be driven by very poor outcomes by patients with unplanned, rescue pVAD.

Five-Year Outcomes after PCI or CABG for Left Main Coronary Disease.

BACKGROUND: Long-term outcomes after percutaneous coronary intervention (PCI) with contemporary drug-eluting stents, as compared with coronary-artery bypass grafting (CABG), in patients with left main coronary artery disease are not clearly established. METHODS: We randomly assigned 1905 patients with left main coronary artery disease of low or intermediate anatomical complexity (according to assessment at the participating centers) to undergo either PCI with fluoropolymer-based cobalt-chromium everolimus-eluting stents (PCI group, 948 patients) or CABG (CABG group, 957 patients). The primary outcome was a composite of death, stroke, or myocardial infarction. RESULTS: At 5 years, a primary outcome event had occurred in 22.0% of the patients in the PCI group and in 19.2% of the patients in the CABG group (difference, 2.8 percentage points; 95% confidence interval [CI], -0.9 to 6.5; P = 0.13). Death from any cause occurred more frequently in the PCI group than in the CABG group (in 13.0% vs. 9.9%; difference, 3.1 percentage points; 95% CI, 0.2 to 6.1). In the PCI and CABG groups, the incidences of definite cardiovascular death (5.0% and 4.5%, respectively; difference, 0.5 percentage points; 95% CI, -1.4 to 2.5) and myocardial infarction (10.6% and 9.1%; difference, 1.4 percentage points; 95% CI, -1.3 to 4.2) were not significantly different. All cerebrovascular events were less frequent after PCI than after CABG (3.3% vs. 5.2%; difference, -1.9 percentage points; 95% CI, -3.8 to 0), although the incidence of stroke was not significantly different between the two groups (2.9% and 3.7%; difference, -0.8 percentage points; 95% CI, -2.4 to 0.9). Ischemia-driven revascularization was more frequent after PCI than after CABG (16.9% vs. 10.0%; difference, 6.9 percentage points; 95% CI, 3.7 to 10.0). CONCLUSIONS: In patients with left main coronary artery disease of low or intermediate anatomical complexity, there was no significant difference between PCI and CABG with respect to the rate of the composite outcome of death, stroke, or myocardial infarction at 5 years. (Funded by Abbott Vascular; EXCEL ClinicalTrials.gov number, NCT01205776.).

Impact of large periprocedural myocardial infarction on mortality after percutaneous coronary intervention and coronary artery bypass grafting for left main disease: an analysis from the EXCEL trial.

AIMS: The prognostic implications of periprocedural myocardial infarction (PMI) after percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) remain controversial. We examined the 3-year rates of mortality among patients with and without PMI undergoing left main coronary artery intervention randomized to PCI with everolimus-eluting stents vs. CABG in the large-scale, multicentre, prospective, randomized EXCEL trial. METHODS AND RESULTS: By protocol, PMI was defined using an identical threshold for PCI and CABG [creatinine kinase-MB (CK-MB) elevation >10× the upper reference limit (URL) within 72 h post-procedure, or >5× URL with new Q-waves, angiographic vessel occlusion, or loss of myocardium on imaging]. Cox proportional hazards modelling was performed controlling for age, sex, hypertension, diabetes mellitus, left ventricular ejection fraction, SYNTAX score, and chronic obstructive pulmonary disease (COPD). A total of 1858 patients were treated as assigned by randomization. Periprocedural MI occurred in 34/935 (3.6%) of patients in the PCI group and 56/923 (6.1%) of patients in the CABG group [odds ratio 0.61, 95% confidence interval (CI) 0.40-0.93; P = 0.02]. Periprocedural MI was associated with SYNTAX score, COPD, cross-clamp duration and total procedure duration, and not using antegrade cardioplegia. By multivariable analysis, PMI was associated with cardiovascular death and all-cause death at 3 years [adjusted hazard ratio (HR) 2.63, 95% CI 1.19-5.81; P = 0.02 and adjusted HR 2.28, 95% CI 1.22-4.29; P = 0.01, respectively]. The effect of PMI was consistent for PCI and CABG for cardiovascular death (Pinteraction = 0.56) and all-cause death (Pinteraction = 0.59). Peak post-procedure CK-MB ≥10× URL strongly predicted mortality, whereas lesser degrees of myonecrosis were not associated with prognosis. CONCLUSION: In the EXCEL trial, PMI was more common after CABG than PCI, and was strongly associated with increased 3-year mortality after controlling for potential confounders. Only extensive myonecrosis (CK-MB ≥10× URL) was prognostically important.

B-Type Natriuretic Peptide Assessment in Patients Undergoing Revascularization for Left Main Coronary Artery Disease: Analysis From the EXCEL Trial.

BACKGROUND: Elevated B-type natriuretic peptide (BNP) is reflective of impaired cardiac function and is associated with worse prognosis among patients with coronary artery disease (CAD). We sought to assess the association between baseline BNP, adverse outcomes, and the relative efficacy of percutaneous coronary intervention (PCI) versus coronary artery bypass grafting (CABG) in patients with left main CAD. METHODS: The EXCEL trial (Evaluation of XIENCE Versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization) randomized patients with left main CAD and low or intermediate SYNTAX scores (Synergy Between PCI With TAXUS and Cardiac Surgery) to PCI with everolimus-eluting stents versus CABG. The primary end point was the composite of all-cause death, myocardial infarction, or stroke. We used multivariable Cox proportional hazards regression to assess the associations between normal versus elevated BNP (≥100 pg/mL), randomized treatment, and the 3-year risk of adverse events. RESULTS: BNP at baseline was elevated in 410 of 1037 (39.5%) patients enrolled in EXCEL. Patients with elevated BNP levels were older and more frequently had additional cardiovascular risk factors and lower left ventricular ejection fraction than those with normal BNP, but had similar SYNTAX scores. Patients with elevated BNP had significantly higher 3-year rates of the primary end point (18.6% versus 11.7%; adjusted hazard ratio [HR], 1.62; 95% confidence interval [CI], 1.16-2.28; P=0.005) and higher mortality (11.5% versus 3.9%; adjusted HR, 2.49; 95% CI, 1.48-4.19; P=0.0006), both from cardiovascular and noncardiovascular causes. In contrast, there were no significant differences in the risks of myocardial infarction, stroke, ischemia-driven revascularization, stent thrombosis, graft occlusion, or major bleeding. A significant interaction ( Pinteraction=0.03) was present between elevated versus normal BNP and treatment with PCI versus CABG for the adjusted risk of the primary composite end point at 3 years among patients with elevated BNP (adjusted HR for PCI versus CABG, 1.54; 95% CI, 0.96-2.47) versus normal BNP (adjusted HR, 0.74; 95% CI, 0.46-1.20). This interaction was stronger when log(BNP) was modeled as a continuous variable ( Pinteraction=0.002). CONCLUSIONS: In the EXCEL trial, elevated baseline BNP levels in patients with left main CAD undergoing revascularization were independently associated with long-term mortality but not nonfatal adverse ischemic or bleeding events. The relative long-term outcomes after PCI versus CABG for revascularization of left main CAD may be conditioned by the baseline BNP level. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01205776.

Everolimus-Eluting Stents or Bypass Surgery for Left Main Coronary Artery Disease.

BACKGROUND: Patients with obstructive left main coronary artery disease are usually treated with coronary-artery bypass grafting (CABG). Randomized trials have suggested that drug-eluting stents may be an acceptable alternative to CABG in selected patients with left main coronary disease. METHODS: We randomly assigned 1905 eligible patients with left main coronary artery disease of low or intermediate anatomical complexity to undergo either percutaneous coronary intervention (PCI) with fluoropolymer-based cobalt-chromium everolimus-eluting stents (PCI group, 948 patients) or CABG (CABG group, 957 patients). Anatomic complexity was assessed at the sites and defined by a Synergy between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery (SYNTAX) score of 32 or lower (the SYNTAX score reflects a comprehensive angiographic assessment of the coronary vasculature, with 0 as the lowest score and higher scores [no upper limit] indicating more complex coronary anatomy). The primary end point was the rate of a composite of death from any cause, stroke, or myocardial infarction at 3 years, and the trial was powered for noninferiority testing of the primary end point (noninferiority margin, 4.2 percentage points). Major secondary end points included the rate of a composite of death from any cause, stroke, or myocardial infarction at 30 days and the rate of a composite of death, stroke, myocardial infarction, or ischemia-driven revascularization at 3 years. Event rates were based on Kaplan-Meier estimates in time-to-first-event analyses. RESULTS: At 3 years, a primary end-point event had occurred in 15.4% of the patients in the PCI group and in 14.7% of the patients in the CABG group (difference, 0.7 percentage points; upper 97.5% confidence limit, 4.0 percentage points; P=0.02 for noninferiority; hazard ratio, 1.00; 95% confidence interval, 0.79 to 1.26; P=0.98 for superiority). The secondary end-point event of death, stroke, or myocardial infarction at 30 days occurred in 4.9% of the patients in the PCI group and in 7.9% in the CABG group (P<0.001 for noninferiority, P=0.008 for superiority). The secondary end-point event of death, stroke, myocardial infarction, or ischemia-driven revascularization at 3 years occurred in 23.1% of the patients in the PCI group and in 19.1% in the CABG group (P=0.01 for noninferiority, P=0.10 for superiority). CONCLUSIONS: In patients with left main coronary artery disease and low or intermediate SYNTAX scores by site assessment, PCI with everolimus-eluting stents was noninferior to CABG with respect to the rate of the composite end point of death, stroke, or myocardial infarction at 3 years. (Funded by Abbott Vascular; EXCEL ClinicalTrials.gov number, NCT01205776 .).

C-reactive protein and prognosis after percutaneous coronary intervention and bypass graft surgery for left main coronary artery disease: Analysis from the EXCEL trial.

BACKGROUND: The prognostic impact of high-sensitivity C-reactive protein (CRP) levels in patients with left main coronary artery disease (LMCAD) treated with percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) is unknown. We sought to determine the effect of elevated baseline CRP levels on the 3-year outcomes after LMCAD revascularization and to examine whether CRP influenced the relative outcomes of PCI versus CABG. METHODS: In the EXCEL trial, patients with LMCAD and Synergy between PCI with Taxus and Cardiac Surgery (SYNTAX) scores ≤32 were randomized to PCI versus CABG. The primary composite outcome of death, myocardial infarction (MI), or stroke was analyzed according to baseline CRP levels. RESULTS: Among 999 patients with available CRP levels, median CRP was 3.10 mg/L (interquartile range 1.12-6.40 mg/L). The rate of the primary composite end point of death, MI, or stroke at 3 years steadily increased with greater baseline CRP levels. The adjusted relationship between the 3-year composite rate of death, MI, or stroke and baseline CRP modeled as a continuous log-transformed variable demonstrated steadily increasing event rates with greater CRP levels (adjusted hazard ratio, 1.26, 95% CI 1.10-1.44, P = .0008). Similarly, patients with CRP ≥10 mg/L had a 3-fold higher risk of the 3-year primary end point compared to patients with lower CRP levels (adjusted hazard ratio 2.92, 95% CI 1.88-4.54, P < .0001). The association between an elevated CRP level and the adjusted 3-year risk of the primary composite end point did not differ according to revascularization strategy (Pinteraction = .75). CONCLUSIONS: In patients with LMCAD undergoing revascularization, elevated baseline CRP levels were strongly associated with subsequent death, MI, and stroke at 3 years, irrespective of the mode of revascularization. Further studies are warranted to determine whether anti-inflammatory therapies may improve the prognosis of high-risk patients with LMCAD following revascularization.

Incidence, Predictors, and Impact of Hospital Readmission After Revascularization for Left Main Coronary Disease.

BACKGROUND: The frequency of and relationship between hospital readmissions and outcomes after revascularization for left main coronary artery disease (LMCAD) are unknown. OBJECTIVES: The purpose of this study was to study the incidence, predictors, and clinical impact of readmissions following percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) for LMCAD. METHODS: In the EXCEL (XIENCE Versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization) trial, 1,905 patients with LMCAD were randomized to PCI vs CABG. The cumulative incidence of readmissions was analyzed with multivariable Anderson-Gill and joint frailty models to account for recurrent events and the competing risk of death. The impact of readmission on subsequent mortality within 5-year follow-up was determined in a time-adjusted Cox proportional hazards model. RESULTS: Within 5 years, 1,868 readmissions occurred in 851 of 1,882 (45.2%) hospital survivors (2.2 ± 1.9 per patient with readmission[s], range 1-16), approximately one-half for cardiovascular causes and one-half for noncardiovascular causes (927 [49.6%] and 941 [50.4%], respectively). One or more readmissions occurred in 463 of 942 (48.6%) PCI patients vs 388 of 940 (41.8%) CABG patients (P = 0.003). After multivariable adjustment, PCI remained an independent predictor of readmission (adjusted HR: 1.22; 95% CI: 1.10-1.35; P < 0.0001), along with female sex, comorbidities, and the extent of CAD. Readmission was independently associated with subsequent all-cause death, with interaction testing indicating a higher risk after PCI than CABG (adjusted HR: 5.72; 95% CI: 3.42-9.55 vs adjusted HR: 2.72; 95% CI: 1.64-4.88, respectively; Pint = 0.03). CONCLUSIONS: In the EXCEL trial, readmissions during 5-year follow-up after revascularization for LMCAD were common and more frequent after PCI than CABG. Readmissions were associated with an increased risk of all-cause death, more so after PCI than with CABG.

Outcomes of Medical Therapy Plus PCI for Multivessel or Left Main CAD Ineligible for Surgery.

BACKGROUND: Percutaneous coronary intervention (PCI) is increasingly used to revascularize patients ineligible for CABG, but few studies describe these patients and their outcomes. OBJECTIVES: This study sought to describe characteristics, utility of risk prediction, and outcomes of patients with left main or multivessel coronary artery disease ineligible for coronary bypass grafting (CABG). METHODS: Patients with complex coronary artery disease ineligible for CABG were enrolled in a prospective registry of medical therapy + PCI. Angiograms were evaluated by an independent core laboratory. Observed-to-expected 30-day mortality ratios were calculated using The Society for Thoracic Surgeons (STS) and EuroSCORE (European System for Cardiac Operative Risk Evaluation) II scores, surgeon-estimated 30-day mortality, and the National Cardiovascular Data Registry (NCDR) CathPCI model. Health status was assessed at baseline, 1 month, and 6 months. RESULTS: A total of 726 patients were enrolled from 22 programs. The mean SYNTAX (Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery) score was 32.4 ± 12.2 before and 15.0 ± 11.7 after PCI. All-cause mortality was 5.6% at 30 days and 12.3% at 6 months. Observed-to-expected mortality ratios were 1.06 (95% CI: 0.71-1.36) with The Society for Thoracic Surgeons score, 0.99 (95% CI: 0.71-1.27) with the EuroSCORE II, 0.59 (95% CI: 0.42-0.77) using cardiac surgeons' estimates, and 4.46 (95% CI: 2.35-7.99) using the NCDR CathPCI score. Health status improved significantly from baseline to 6 months: SAQ summary score (65.9 ± 22.5 vs 86.5 ± 15.1; P < 0.0001), Kansas City Cardiomyopathy Questionnaire summary score (54.1 ± 27.2 vs 82.6 ± 19.7; P < 0.0001). CONCLUSIONS: Patients ineligible for CABG who undergo PCI have complex clinical profiles and high disease burden. Following PCI, short-term mortality is considerably lower than surgeons' estimates, similar to surgical risk model predictions but is over 4-fold higher than estimated by the NCDR CathPCI model. Patients' health status improved significantly through 6 months.

Impact of Periprocedural Adverse Events After PCI and CABG on 5-Year Mortality: The EXCEL Trial.

BACKGROUND: The relative risks for different periprocedural major adverse events (MAE) after percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) on subsequent mortality have not been described. OBJECTIVES: The aim of this study was to assess the association between periprocedural MAE occurring within 30 days postprocedure and early and late mortality after left main coronary artery revascularization by PCI and CABG. METHODS: In the EXCEL (Evaluation of XIENCE Versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization) trial, patients with left main disease were randomized to PCI vs CABG. The associations between 12 prespecified nonfatal MAE and subsequent 5-year all-cause and cardiovascular death in 1,858 patients were examined using logistic regression. RESULTS: One or more nonfatal MAE occurred in 111 of 935 patients (11.9%) after PCI and 419 of 923 patients (45.4%) after CABG (P < 0.0001). Patients with MAE were older and had more baseline comorbidities. Within 5 years, all-cause death occurred in 117 and 87 patients after PCI and CABG, respectively. Experiencing an MAE was a strong independent predictor of 5-year mortality after both PCI (adjusted OR: 4.61; 95% CI: 2.71-7.82) and CABG (adjusted OR: 3.25; 95% CI: 1.95-5.41). These associations were present within the first 30 days and between 30 days and 5 years postprocedure. Major or minor bleeding with blood transfusion ≥2 U was an independent predictor of 5-year mortality after both procedures. Stroke, unplanned revascularization for ischemia, and renal failure were significantly associated with mortality only after CABG. CONCLUSIONS: In the EXCEL trial, nonfatal periprocedural MAE were strongly associated with early and late mortality after both PCI and CABG for left main disease.

Fusion of Bovine Tissue Aortic Valve Leaflets in a Patient With Left Ventricular Assist Device.

Patients with both a prosthetic aortic valve and prolonged left ventricular assist device support can develop rapid deterioration of their valve prosthesis. In patients with myocardial recovery who are undergoing explantation of their ventricular assist device, preoperative and intraoperative evaluation of the valve prosthesis should be performed to ensure adequate function. (Level of Difficulty: Advanced.).

Impact of renin-angiotensin system inhibitors after revascularization of patients with left main coronary artery disease.

BACKGROUND: There is a paucity of data regarding the effect of inhibition of the renin-angiotensin system on outcomes after percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG). We sought to examine long-term outcomes of patients with left main coronary disease (LMCAD) randomized to PCI with fluoropolymer-based cobalt-chromium everolimus-eluting stents or CABG according to treatment at discharge with angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) in the large-scale, multicenter, randomized EXCEL trial. METHODS: EXCEL randomized 1905 patients with LMCAD of low and intermediate anatomical complexity (visually-assessed SYNTAX score ≤32) to PCI (n = 948) versus CABG (n = 957). Patients were categorized according to whether they were treated with ACEI/ARB at discharge; their outcomes from discharge to 5 years were examined using multivariable logistic regression with an offset for follow-up time. RESULTS: Among 1775 patients discharged alive with known ACEI/ARB treatment status, 896 (50.5%) were treated with one of these agents. Among those treated with ACEI/ARB, the 5-year rate of all-cause death was similar after PCI or CABG (10.7% versus 9.8% respectively, adjOR, 0.94; 95% CI, 0.56-1.57) in contrast to patients not treated with ACEI/ARB (15.0% versus 7.8%, respectively, adjOR, 2.20; 95% CI, 1.32-3.67) (Pinteraction = 0.02). Significant interactions between treatment arm (PCI versus CABG) and ACEI/ARB treatment status were also found for cardiovascular death (Pinteraction = 0.03), ischemia-driven revascularization (Pinteraction = 0.03), target vessel revascularization (Pinteraction = 0.007) and target vessel failure (Pinteraction = 0.0009). CONCLUSION: In the EXCEL trial, the postdischarge rates of death and revascularization after 5 years were similar after PCI and CABG in patients with LMCAD treated with ACEI/ARB at discharge. In contrast, event rates were higher after PCI versus CABG in those not so treated.

Geographical variations in left main coronary artery revascularisation: a prespecified analysis of the EXCEL trial.

BACKGROUND: The EXCEL trial reported similar five-year rates of the primary composite outcome of death, myocardial infarction (MI), or stroke after percutaneous coronary intervention (PCI) compared with coronary artery bypass grafting (CABG) for treatment of obstructive left main coronary artery disease (LMCAD). AIMS: We sought to determine whether these outcomes remained consistent regardless of geography of enrolment. METHODS: We performed a prespecified subgroup analysis based on regional enrolment. RESULTS: Among 1,905 patients randomised to PCI (n=948) or CABG (n=957), 1,075 (56.4%) were recruited at 52 European Union (EU) centres, and 752 (39.5%) were recruited at 67 North American (NA) centres. EU versus NA patients varied according to numerous baseline demographics, anatomy, pharmacotherapy and procedural characteristics. Nonetheless, the relative rates of the primary endpoint after PCI versus CABG were consistent across EU versus NA centres at 30 days and 5 years. However, NA participants had substantially higher late rates of ischaemia-driven revascularisation (IDR) after PCI, driven predominantly by the need for greater target vessel and lesion revascularisation. This culminated in a significant difference in the relative risk of the secondary composite outcome of death, MI, stroke, or IDR at 5 years (pinteraction=0.02). CONCLUSIONS: In the EXCEL trial, the relative risks for the 30-day and five-year primary composite outcome of death, MI or stroke after PCI versus CABG were consistent irrespective of geography. However, five-year rates of IDR after PCI were significantly higher in NA centres, a finding the Heart Team and patients should consider when making treatment decisions. ClinicalTrials.gov identifier: NCT01205776.

The Outcomes of Percutaneous RevascularizaTIon for Management of SUrgically Ineligible Patients With Multivessel or Left Main Coronary Artery Disease (OPTIMUM) Registry: Rationale and Design.

BACKGROUND: Guidelines endorse coronary artery bypass as the preferred revascularization strategy for patients with left main and/or multivessel coronary artery disease (CAD). However, many patients are deemed excessively high risk for surgery after Heart Team evaluation. No prospective studies have examined contemporary treatment patterns, rationale for surgical decision-making, completeness of revascularization with percutaneous coronary intervention (PCI), and outcomes in this high-risk population with advanced CAD. METHODS: We designed the Outcomes of Percutaneous RevascularizaTIon for Management of SUrgically Ineligible Patients with Multivessel or Left Main Coronary Artery Disease (OPTIMUM) registry, a prospective, multicenter study of patients with "surgical anatomy" determined to be at prohibitive risk for bypass surgery. The primary outcome is comparison of observed to predicted 30-day mortality, with secondary outcomes of patient-reported health status and the association between completeness of revascularization and clinical outcomes. Patient characteristics driving surgical risk determinations will be reported, and peri-operative risk will be assessed using validated scoring methods. Angiograms will be assessed by an independent core laboratory, and clinical events will be adjudicated. RESULTS: Clinical outcomes assessments will include 30-day and 1-year cardiovascular events, health status at 1, 6 and 12-months, and 5-year mortality. CONCLUSIONS: OPTIMUM is the first prospective, multicenter study to examine treatment strategies and outcomes among multivessel CAD patients deemed ineligible for surgical revascularization after Heart Team assessment. This registry will provide unique insights into the clinical decision-making, revascularization practices, safety, effectiveness, and health status outcomes in this high-risk population.

Safety, efficacy, and hemodynamic performance of a stented bovine pericardial aortic valve bioprosthesis: Two-year analysis.

OBJECTIVES: The study objectives were to evaluate the safety, efficacy, and hemodynamic performance of a novel stented bovine pericardial aortic valve bioprosthesis 2 years after implantation. METHODS: The PERIcardial SurGical AOrtic Valve ReplacemeNT Pivotal Trial enrolled patients with symptomatic moderate/severe aortic stenosis or regurgitation at centers in Canada, Europe, and the United States. We report the outcomes and hemodynamic performance in patients with up to 2 years of follow-up. RESULTS: A total of 1273 patients were enrolled, and 1110 underwent implantation. Among patients undergoing implantation, the mean age was 70.2 ± 8.9 years; 833 (75.0%) were male. Risk of mortality (Society of Thoracic Surgeons) was 2.0% ± 1.4%. At the time of analysis, 604 patients had completed the 2-year follow-up visit. Linearized late event rates were as follows: all death, 2.68%; valve-related death, 0.42%; valve thrombosis, 0.05%; endocarditis, 0.94%; thromboembolism, 1.68%; all hemorrhage, 2.94%; major hemorrhage, 1.99%; all paravalvular leak, 0.26%; and major paravalvular leak, 0.05% per patient-year. Mean 2-year aortic gradient and effective orifice area were 13.4 ± 5.0 mm Hg and 1.5 ± 0.37 cm2, respectively. Moderate and severe prosthesis-patient mismatch were observed in 43.5% and 34.8% of patients at 2 years, respectively. Improvement in New York Heart Association class compared with baseline was observed in 73.0% with moderate mismatch and 74.1% with severe mismatch. CONCLUSIONS: The Avalus (Medtronic, Minneapolis, Minn) bovine pericardial valve demonstrates good clinical and safety outcomes at 2 years. Hemodynamic performance shows mean gradients comparable to currently available bovine pericardial aortic valves. There was no clinical impact of moderate to severe mismatch at 2 years. Further follow-up is required to evaluate midterm to long-term clinical outcome.

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

BACKGROUND: Varying definitions of procedural myocardial infarction (PMI) are in widespread use. OBJECTIVES: This 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. METHODS: The 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. RESULTS: PMIProt 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. CONCLUSIONS: The 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).

Off-Pump Versus On-Pump Bypass Surgery for Left Main Coronary Artery Disease.

BACKGROUND: Concerns remain for a greater risk of incomplete revascularization and reduced survival with off-pump coronary artery bypass grafting (CABG) surgery compared with on-pump surgery particularly in patients with left main disease and extensive underlying myocardial ischemia. OBJECTIVES: This study sought to compare outcomes following off-pump versus on-pump surgery for left main disease by performing a post hoc analysis from the multicenter, randomized EXCEL (Evaluation of XIENCE versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization) trial. METHODS: The EXCEL trial was designed to compare percutaneous coronary intervention with everolimus-eluting stents versus CABG in patients with left main disease. CABG was performed with or without cardiopulmonary bypass (on-pump vs. off-pump surgery) according to the discretion of the operator. The 3-year outcomes in the off-pump and on-pump groups were compared using inverse probability of treatment weighting (IPTW) for treatment effect estimation. RESULTS: Among 923 CABG patients, 652 and 271 patients underwent on-pump and off-pump surgery, respectively. Despite a similar extent of disease, off-pump surgery was associated with a lower rate of revascularization of the left circumflex coronary artery (84.1% vs. 90.0%; p = 0.01) and right coronary artery (31.1% vs. 40.6%; p = 0.007). After IPTW adjustment for baseline differences, off-pump surgery was associated with a significantly increased risk of 3-year all-cause death (8.8% vs. 4.5%; hazard ratio: 1.94; 95% confidence interval: 1.10 to 3.41; p = 0.02) and a nonsignificant difference in the risk for the composite endpoint of death, myocardial infarction, or stroke (11.8% vs. 9.2%; hazard ratio: 1.28; 95% confidence interval: 0.82 to 2.00; p = 0.28). CONCLUSIONS: Among patients with left main disease treated with CABG in the EXCEL trial, off-pump surgery was associated with a lower rate of revascularization of the coronary arteries supplying the inferolateral wall and an increased risk of 3-year all-cause death compared with on-pump surgery.

Outcomes following surgical revascularization with single versus bilateral internal thoracic arterial grafts in patients with left main coronary artery disease undergoing coronary artery bypass grafting: insights from the EXCEL trial†.

OBJECTIVES: Observational data suggest that the use of a single internal thoracic artery (SITA) may result in inferior outcomes compared with bilateral internal thoracic artery (BITA) use for coronary artery bypass grafting (CABG)-a finding not yet supported by randomized trial outcomes. However, the optimal number of internal thoracic artery grafts in patients with left main coronary artery disease has not been investigated. METHODS: The EXCEL trial randomized 1905 patients with left main coronary artery disease to percutaneous coronary intervention with everolimus-eluting stents versus CABG. Among the 905 patients undergoing CABG, 688 (76.0%) received SITA and 217 (24.0%) received BITA. Differences in clinical event rates were estimated using the Kaplan-Meier method and compared with the log-rank test. Multivariable Cox regression was used to adjust for differences in baseline covariates. RESULTS: Compared to SITA, patients treated with BITA were younger (66.1 ± 9.5 vs 64.5 ± 9.3 years, P = 0.020), were less likely female (24.3% vs 14.3%, P = 0.002) and diabetic (28.8% vs 15.2%, P < 0.001), and had a lower prevalence of peripheral vessel disease (10.2% vs 5.5%, P = 0.040). The unadjusted 3-year composite primary endpoint of death, stroke or myocardial infarction (MI) occurred in 15.6% of SITA vs 11.6% of BITA patients (P = 0.17). The SITA group tended to have a higher 3-year rate of all-cause death compared with the BITA group (6.7% vs 3.3%; P = 0.070). Stroke, MI and ischaemia-driven revascularization outcomes were not significantly different between groups. After adjusting for baseline differences, neither the composite of death, stroke or MI [hazard ratio (HR) 1.12, 95% confidence interval (CI) 0.71-1.78; P = 0.62] nor mortality (HR 1.36, 95% CI 0.60-3.12; P = 0.46) was significantly higher with SITA. The rehospitalization rate after 3 years was higher in the SITA group (35.8% vs 26.0%, P = 0.008), a difference which was no longer present after multivariable adjustment (HR 1.27, 95% CI 0.93-1.74; P = 0.13). Sternal wound dehiscence within 30 days did not occur more often in the BITA group compared to the SITA group (1.8% vs 2.2%, P > 0.99). CONCLUSIONS: In the EXCEL trial, there were no clinical differences at 3 years between SITA or BITA revascularization in patients with left main coronary artery disease.

Outcomes After Left Main Percutaneous Coronary Intervention Versus Coronary Artery Bypass Grafting According to Lesion Site: Results From the EXCEL Trial.

OBJECTIVES: The authors sought to determine the extent to which the site of the left main coronary artery (LM) lesion (distal bifurcation versus ostial/shaft) influences the outcomes of revascularization with percutaneous coronary intervention (PCI) versus coronary artery bypass grafting (CABG). BACKGROUND: Among 1,905 patients with LM disease and site-assessed SYNTAX scores of <32 randomized in the EXCEL (Evaluation of XIENCE Versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization) trial, revascularization with PCI and CABG resulted in similar rates of the composite primary endpoint of death, myocardial infarction (MI), or stroke at 3 years. METHODS: Outcomes from the randomized EXCEL trial were analyzed according to the presence of angiographic core laboratory-determined diameter stenosis ≥50% involving the distal LM bifurcation (n = 1,559; 84.2%) versus disease isolated to the LM ostium or shaft (n = 293; 15.8%). RESULTS: At 3 years, there were no significant differences between PCI and CABG for the primary composite endpoint of death, MI, or stroke for treatment of both distal LM bifurcation disease (15.6% vs. 14.9%, odds ratio [OR]: 1.08, 95% confidence interval [CI]: 0.81 to 1.42; p = 0.61) and isolated LM ostial/shaft disease (12.4% vs. 13.5%, OR: 0.90, 95% CI: 0.45 to 1.81; p = 0.77) (pinteraction = 0.65). However, at 3 years, ischemia-driven revascularization occurred more frequently after PCI than CABG in patients with LM distal bifurcation disease (13.0% vs. 7.2%, OR: 2.00, 95% CI: 1.41 to 2.85; p = 0.0001), but were not significantly different in patients with disease only at the LM ostium or shaft (9.7% vs. 8.4%, OR: 1.18, 95% CI: 0.52 to 2.69; p = 0.68) (pinteraction = 0.25). CONCLUSIONS: In the EXCEL trial, PCI and CABG resulted in comparable rates of death, MI, or stroke at 3 years for treatment of LM disease, including those with distal LM bifurcation disease. Repeat revascularization rates during follow-up after PCI compared with CABG were greater for lesions in the distal LM bifurcation but were similar for disease isolated to the LM ostium or shaft.

Quality-of-Life After Everolimus-Eluting Stents or Bypass Surgery for Left-Main Disease: Results From the EXCEL Trial.

BACKGROUND: The EXCEL (Evaluation of Xience Versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization) trial compared outcomes in patients with unprotected left main coronary artery disease (LMCAD) treated with coronary artery bypass graft (CABG) or percutaneous coronary intervention (PCI) using everolimus-eluting stents. Whereas rates of death, stroke, and myocardial infarction were similar at 36 months, event timing and repeat revascularization rates differed by treatment group. OBJECTIVES: To understand the effects of revascularization strategy from the patient's perspective, a prospective quality of life (QoL) substudy was performed alongside the EXCEL trial. METHODS: Between September 2010 and March 2014, 1,905 patients with LMCAD were randomized to undergo CABG or PCI, of whom 1,788 participated in the QoL substudy. QoL was assessed at baseline and 1, 12, and 36 months using the Seattle Angina Questionnaire, the 12-Item Short Form Health Survey, the Rose Dyspnea Scale, the Patient Health Questionnaire-8, and the EQ-5D. Differences between PCI and CABG were assessed using longitudinal random-effect growth curve models. RESULTS: Over 36 months, both PCI and CABG were associated with significant improvements in QoL compared with baseline. At 1 month, PCI was associated with better QoL than CABG. By 12 months though, these differences were largely attenuated, and by 36 months, there were no significant QoL differences between PCI and CABG. CONCLUSIONS: Among selected patients with LMCAD, both PCI and CABG result in similar QoL improvement through 36 months, although a greater early benefit is seen with PCI. Taken together with the 3-year clinical results of EXCEL, these findings suggest that PCI and CABG provide similar intermediate-term outcomes for patients with LMCAD. (Evaluation of Xience Versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization [EXCEL]; NCT01205776).