Impact of Procedural Success Definitions on Long-Term Outcomes in Patients With Rheumatic Mitral Stenosis Treated With Percutaneous Balloon Mitral Valvuloplasty: A Multicenter, Retrospective Cohort Study.

BACKGROUND: It is uncertain which percutaneous balloon mitral valvuloplasty (PBMV) success definitions should be used because there are no studies comparing the effects of these definitions on subsequent outcomes. We evaluated the association between 3 success definitions and long-term clinical outcomes in patients with rheumatic mitral stenosis who underwent PBMV. METHODS AND RESULTS: This multicenter retrospective study included patients with severe rheumatic mitral stenosis who underwent PBMV. Three definitions were used as follows: (A) post-PBMV mitral valve area (MVA) ≥1.5 cm2 or ≥50% increase in MVA with MR <3+; (B) post-PBMV MVA ≥1.5 cm2 and MR ≤2+; and (C) post-PBMV MVA ≥1.5 cm2 or ≥50% increase in MVA, with no more than 1-grade increment in MR. Multivariable Cox regression analyses were performed to evaluate the associations between PBMV success and the composite of all-cause mortality, mitral surgery, and repeat PBMV. Successful PBMV, according to definitions A, B, and C was associated with a lower risk of the composite outcomes (definition A-hazard ratio [HR], 0.55 [95% CI, 0.43-0.69], definition B-HR, 0.55 [95% CI, 0.43-0.69], definition C-HR, 0.55 [95% CI, 0.44-0.69]). Patients meeting all 3 success definitions had the lowest risk compared with those who did not meet any definition or met 1 or 2 definitions. CONCLUSIONS: All 3 success definitions had a prognostic impact on outcomes. Patients who achieved post-PBMV MVA ≥1.5 cm2, irrespective of the percentage increase in MVA, and MR ≤grade 2, with no more than a 1-grade increment in MR, had the most favorable outcomes.

Association of myosteatosis with treatment response and survival in patients with hepatocellular carcinoma undergoing chemoembolization: a retrospective cohort study.

Patients with hepatocellular carcinoma (HCC) have poor prognosis and have frequent treatment-related toxicities resulting in cancer-associated cachexia. This study aimed to determine the association of myosteatosis and sarcopenia on mortality in patients with HCC treated with transarterial chemoembolization (TACE). Six hundred and eleven patients diagnosed with HCC and underwent TACE at a tertiary care center between 2008 and 2019 were included. Body composition was assessed using axial CT slices at level L3 to calculate the skeletal muscle density for myosteatosis and skeletal muscle index for sarcopenia. The primary outcome was overall survival while the secondary outcome was TACE response. Patients with myosteatosis had a poorer TACE response than patients without myosteatosis (56.12% vs. 68.72%, adjusted odds ratio [OR] 0.49, 95% confidence interval [CI] 0.34-0.72). The rate of TACE response in patients with sarcopenia was not different from those without sarcopenia (60.91% vs. 65.22%, adjusted OR 0.79, 95% CI 0.55-1.13). Patients with myosteatosis had shorter overall survival than without myosteatosis (15.9 vs. 27.1 months, P < 0.001). In the multivariable Cox regression analysis, patients with myosteatosis or sarcopenia had higher risk of all-cause mortality than their counterparts (adjusted hazard ratio [HR] for myosteatosis versus no myosteatosis 1.66, 95% CI 1.37-2.01, adjusted HR for sarcopenia versus no sarcopenia 1.26, 95% CI 1.04-1.52). Patients with both myosteatosis and sarcopenia had the highest 7 year mortality rate at 94.45%, while patients with neither condition had the lowest mortality rate at 83.31%. The presence of myosteatosis was significantly associated with poor TACE response and reduced survival. Identifying patients with myosteatosis prior to TACE could allow for early interventions to preserve muscle quality and might improve prognosis in HCC patients.

Predicting Infection Related Complications After Endovascular Repair of Infective Native Aortic Aneurysms.

OBJECTIVE: Endovascular aortic repair (EVAR) as surgical treatment for infective native aortic aneurysm (INAA) is associated with superior survival compared with open surgery, but with the risk of infection related complications (IRCs). This study aimed to assess the association between baseline clinical and computed tomography (CT) features and the risk of post-operative IRCs in patients treated with EVAR for INAA. It also sought to develop a model to predict long term IRCs in patients with abdominal INAA treated with EVAR. METHODS: All initial clinical details and CT examinations of INAAs between 2005 and 2020 at a major referral hospital were reviewed retrospectively. The images were scrutinised according to aneurysm features, as well as peri-aortic and surrounding organ involvement. Data on post-operative IRCs were found in the patient records. Cox regression analysis was used to derive predictors for IRCs and develop a model to predict five year IRCs after EVAR in abdominal INAA. RESULTS: Of 3 780 patients with the diagnosis of aortic aneurysm or aortitis, 98 (3%) patients were treated with EVAR for abdominal INAAs and were thus included. The mean follow up time was 52 months (range 0 ‒ 163). The mean transaxial diameter was 6.5 ± 2.4 cm (range 2.1 ‒14.7). In the enrolled patients, 38 (39%) presented with rupture. The five year IRC rate in abdominal INAAs was 26%. Female sex, renal insufficiency, positive blood culture, aneurysm diameter, and psoas muscle involvement were predictive of five year IRC in abdominal INAA after EVAR. The model had a C-index of 0.76 (95% CI 0.66 - 0.87). CONCLUSION: Pre-operative clinical and CT features have the potential to predict IRC after endovascular aortic repair in INAA patients. These findings stress the importance of rigorous clinical, laboratory, and radiological follow up in these patients.

Prognostic Value of Ankle-Brachial Index in Prediction of Cardiovascular Events in an Asian Population with Multiple Atherosclerotic Risk Factors.

We aimed to evaluate the incremental prognostic value after incorporation of the ankle-brachial index (ABI) into the 10-year pool cohort equation (PCE) risk model in patients with multiple risk factors (MRFs). A total of 4332 MRFs patients were divided into 2 groups as ABI ≤.9 or >.9. The primary outcome was hard cardiovascular events (hCVE: including cardiovascular death, myocardial infarction, or ischemic stroke) over a median follow-up of 36 months. The Cox proportional hazards survival model, C-statistic, and net reclassification indices (NRI) were used. The occurrence of the primary outcome in the ABI ≤.9 group (3.7%) was significantly greater than in the ABI > .9 group (1.3%), P < .001. ABI is an independent predictor of hCVE in addition to the variables in the standard risk model (age, gender, and smoking status). ABI modestly improved the C-index when added to the PCE risk model (PCE .70 vs ABI+PCE .74). The addition of ABI to the PCE risk model did not significantly improve the classification of patients (NRI -.029; 95% CI: -.215 to .130). Despite ABI being one of the independent predictors of hCVE, integration of ABI into the PCE model did not improve the efficacy of risk reclassification in patients with MRFs.

Procedural success and outcomes after percutaneous balloon mitral valvuloplasty in rheumatic mitral stenosis with moderate mitral regurgitation: a retrospective cohort study.

Background: Percutaneous balloon mitral valvuloplasty (PBMV) is contraindicated in mitral stenosis (MS) with moderate mitral regurgitation (MR) according to the European guidelines. However, small-sized studies have demonstrated the feasibility and safety of PBMV in these patients. We aimed to study the procedural success and mid-term outcomes of PBMV in MS patients with moderate MR. Methods: The present study was a retrospective cohort study in consecutive patients with severe rheumatic MS who underwent PBMV with the Inoue technique in Songklanagarind hospital. The severity of mitral regurgitation was assessed with qualitative Doppler. The patients were grouped according to their MR severity before PBMV into moderate MR or less-than-moderate MR. Procedural success and a composite of all-cause death, mitral valve surgery or re-PBMV were compared between the two groups. Results: Of 618 patients with rheumatic MS who underwent PBMV in Songklanagarind hospital between January 2003 and October 2020, 598 patients (96.8%) had complete information of pre-PBMV MR severity and procedural success. Forty-nine patients (8.2%) had moderate MR before PBMV. Moderate MR before PBMV was not associated with a lower chance of PBMV success (moderate MR vs. less-than-moderate MR before PBMV; adjusted OR 0.65, 95% CI: 0.32-1.29, P=0.22). Survival probability of all-cause death, MV surgery or re-PBMV in the group with moderate MR before PBMV was not different from the group with less-than-moderate MR (adjusted HR 1.30, 95% CI: 0.98-1.62, P=0.10). Conclusions: PBMV is an effective and safe treatment in rheumatic MS with moderate MR.

Predicting mortality in cardiac care unit patients: external validation of the Mayo cardiac intensive care unit admission risk score.

AIMS: The Mayo Cardiac Intensive Care Unit Admission Risk Score (M-CARS) had excellent performance in predicting in-hospital mortality in the US population. We sought to validate the M-CARS for in-hospital and post-discharge mortality in Asian patients admitted to the cardiac care unit (CCU). METHODS AND RESULTS: Patients admitted to the CCU of a tertiary care centre between July 2015 and December 2019 were included into the study. Patients with intra-hospital transfer to the CCU due to intensive care unit overflow, postoperative cardiac surgery, or for monitoring after elective procedures were excluded. Cardiac arrest, cardiogenic shock, respiratory failure, Braden skin score, blood urea nitrogen, anion gap, and red cell distribution width, were used to calculate the M-CARS. Patients were stratified into three groups, according to the M-CARS (<2, 2-6, >6). Of 1988 patients in the study, 30.1% were female with a median age of 65 years. Prevalence of cardiogenic shock and respiratory failure at admission were 2.8% and 4.5%, respectively. One hundred and seventeen patients died during the admission (mortality rate of 5.9%). The in-hospital mortality rate in patients with M-CARS of <2, 2-6, and >6 was 1.1%, 9.8%, and 35.5%, respectively. C-statistic of M-CARS for in-hospital mortality was 0.840 (95% CI 0.805-0.873); whereas, it was 0.727 (95% CI 0.690-0.761) for 1-year post-discharge mortality. Calibration plot showed good agreement between predicted and observed in-hospital mortality in the majority of patients. CONCLUSIONS: The M-CARS was useful in our study, in terms of discrimination and calibration. M-CARS identified high-risk patients in CCU, who had unacceptably high mortality rate during hospital stay and thereafter.

Usefulness of the updated logistic clinical SYNTAX score after percutaneous coronary intervention in patients with prior coronary artery bypass graft surgery: Insights from the GLOBAL LEADERS trial.

OBJECTIVES: We aimed to investigate the prognostic utility of the anatomical CABG SYNTAX and logistic clinical SYNTAX scores for mortality after percutaneous coronary intervention (PCI) in patients with prior coronary artery bypass grafts (CABG). BACKGROUND: The anatomical SYNTAX score evaluated the anatomical complexity of coronary artery disease and helped predict the prognosis of patients undergoing PCI. The anatomical CABG SYNTAX score was derived from the anatomical SYNTAX score in patients with prior CABG, whilst the logistic clinical SYNTAX score was developed by incorporating clinical factors into the anatomical SYNTAX score. METHODS: We calculated the anatomical CABG SYNTAX score and logistic clinical SYNTAX score in 205 patients in the GLOBAL LEADERS trial. The predictive abilities of these scores for 2-year all-cause mortality were evaluated. RESULTS: Using the median scores as categorical thresholds between low and high score groups, the logistic clinical SYNTAX score was able to discriminate the risk of 2-year mortality, unlike the anatomical CABG SYNTAX score. The logistic clinical SYNTAX was significantly better at predicting 2-year mortality, compared to the anatomical CABG SYNTAX score, as evidenced by AUC values in receiver-operating characteristic curve analysis (0.806 vs. 0.582, p < .001) and integrated discrimination improvement (0.121, p < .001). CONCLUSIONS: The logistic clinical SYNTAX score was superior to the anatomical CABG SYNTAX score in predicting 2-year mortality.

Impact of renal function on clinical outcomes after PCI in ACS and stable CAD patients treated with ticagrelor: a prespecified analysis of the GLOBAL LEADERS randomized clinical trial.

BACKGROUND: Impaired renal function (IRF) is associated with increased risks of both ischemic and bleeding events. Ticagrelor has been shown to provide greater absolute reduction in ischemic risk following acute coronary syndrome (ACS) in those with versus without IRF. METHODS: A pre-specified sub-analysis of the randomized GLOBAL LEADERS trial (n = 15,991) comparing the experimental strategy of 23-month ticagrelor monotherapy (after 1-month ticagrelor and aspirin dual anti-platelet therapy [DAPT]) with 12-month DAPT followed by 12-month aspirin after percutaneous coronary intervention (PCI) in ACS and stable coronary artery disease (CAD) patients stratified according to IRF (glomerular filtration rate < 60 ml/min/1.73 m2). RESULTS: At 2 years, patients with IRF (n = 2171) had a higher rate of the primary endpoint (all-cause mortality or centrally adjudicated, new Q-wave myocardial infarction [MI](hazard ratio [HR] 1.64, 95% confidence interval [CI] 1.35-1.98, padj = 0.001), all-cause death, site-reported MI, all revascularization and BARC 3 or 5 type bleeding, compared with patients without IRF. Among patients with IRF, there were similar rates of the primary endpoint (HR 0.82, 95% CI 0.61-1.11, p = 0.192, pint = 0.680) and BARC 3 or 5 type bleeding (HR 1.10, 95% CI 0.71-1.71, p = 0.656, pint = 0.506) in the experimental versus the reference group. No significant interactions were seen between IRF and treatment effect for any of the secondary outcome variables. Among ACS patients with IRF, there were no between-group differences in the rates of the primary endpoint or BARC 3 or 5 type bleeding; however, the rates of the patient-oriented composite endpoint (POCE) of all-cause death, any stroke, MI, or revascularization (pint = 0.028) and net adverse clinical events (POCE and BARC 3 or 5 type bleeding) (pint = 0.045), were lower in the experimental versus the reference group. No treatment effects were found in stable CAD patients categorized according to presence of IRF. CONCLUSIONS: IRF negatively impacted long-term prognosis after PCI. There were no differential treatment effects found with regard to all-cause death or new Q-wave MI after PCI in patients with IRF treated with ticagrelor monotherapy. CLINICAL TRIAL REGISTRATION: The trial has been registered with ClinicalTrials.gov, number NCT01813435.

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.

OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Impact of established cardiovascular disease on outcomes in the randomized global leaders trial.

OBJECTIVE: To investigate the impact of different anti-platelet strategies on outcomes after percutaneous coronary intervention (PCI) in patients with established cardiovascular disease (CVD). METHODS: GLOBAL LEADERS was a randomized, superiority, all-comers trial comparing one-month dual anti-platelet therapy (DAPT) with ticagrelor and aspirin followed by 23-month ticagrelor monotherapy (experimental treatment) with standard 12-month DAPT followed by 12-month aspirin monotherapy (reference treatment) in patients treated with a biolimus A9-eluting stent. Established CVD was defined as ≥1 prior myocardial infarction, PCI, coronary artery bypass operation, stroke, or established peripheral vascular disease. The primary endpoint was a composite of all-cause death or new Q-wave MI at 2-years. The secondary safety endpoint was BARC 3 or 5 bleeding. Exploratory secondary endpoints were the patient-orientated composite endpoint and net adverse clinical events. RESULTS: Among the 15,761 patients in this cohort were 6,693 patients (42.5%) with established CVD. Compared to those without established CVD, these patients had significantly higher rates of the primary (5.1 vs. 3.3%, HR1.59[1.36-1.86], p < .001) and secondary composite endpoints with no significant differences in bleeding. There was a nonsignificant reduction in the primary endpoint in patients with established CVD receiving the experimental treatment (4.6 vs. 5.6%, HR0.82[0.66-1.02], p = .07). When comparing patients without CVD to those with one or three territories of CVD, the hazard ratio for the primary endpoint increased in unadjusted and adjusted models. CONCLUSIONS: The poorer outcomes in patients with established CVD are not mitigated by prolonged monotherapy with a potent P2Y12 inhibitor suggesting a greater need to focus on modifiable risk factors.

Ticagrelor monotherapy beyond one month after PCI in ACS or stable CAD in elderly patients: a pre-specified analysis of the GLOBAL LEADERS trial.

AIMS: Antiplatelet treatment in the elderly post percutaneous coronary interventions (PCI) remains a complex issue. Here we report the results of the pre-specified subgroup analysis of the GLOBAL LEADERS trial evaluating the long-term safety and cardiovascular efficacy of ticagrelor monotherapy among patients categorised according to the pre-specified cut-off value of 75 years of age. METHODS AND RESULTS: This was a pre-specified analysis of the randomised GLOBAL LEADERS trial (n=15,991), comparing 23-month ticagrelor monotherapy (after one month of DAPT) with the reference treatment (12-month DAPT followed by 12 months of aspirin). Among elderly patients (>75 years; n=2,565), the primary endpoint (two-year all-cause mortality or new Q-wave core lab-adjudicated myocardial infarction [MI]) occurred in 7.2% and 9.4% of patients in the ticagrelor monotherapy and the reference group, respectively (hazard ratio [HR] 0.75, 95% confidence interval [CI]: 0.58-0.99, p=0.041; pint=0.23); BARC-defined bleeding type 3/5 occurred in 5.2% and 4.1%, respectively (HR 1.29, 95% CI: 0.89-1.86; p=0.180; pint=0.06). The elderly with stable CAD had a higher rate of BARC 3/5 type bleeding (HR 2.05, 95% CI: 1.18-3.55) with ticagrelor monotherapy versus the reference treatment (pint=0.02). Elderly patients had a lower rate of definite or probable stent thrombosis (ST) with ticagrelor monotherapy (0.4% vs 1.4%, p=0.015, pint=0.01), compared with the reference group. CONCLUSIONS: In this pre-specified, exploratory analysis of the overall neutral trial, there was no differential treatment effect of ticagrelor monotherapy (after one-month dual therapy with aspirin) found in elderly patients undergoing PCI with respect to the rate of the primary endpoint of all-cause death or new Q-wave MI. The lower rate of ST in the elderly with ticagrelor monotherapy is hypothesis-generating. ClinicalTrials.gov identifier: NCT01813435.

Clinical relevance of ticagrelor monotherapy following 1-month dual antiplatelet therapy after bifurcation percutaneous coronary intervention: Insight from GLOBAL LEADERS trial.

BACKGROUND: The aim of this study was to investigate the impact of ticagrelor monotherapy following 1-month dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) for bifurcation lesions. METHODS: GLOBAL LEADERS was a randomized, superiority, all-comers trial comparing 1-month DAPT with ticagrelor and aspirin followed by 23-month ticagrelor monotherapy (experimental treatment) with standard 12-month DAPT followed by 12-month aspirin monotherapy (reference treatment) in patients treated with a biolimus A9-eluting stent. The primary endpoint was a composite of all-cause death or new Q-wave myocardial infarction (MI) at 2 years. RESULTS: Among the 15,845 patients included in this subgroup analysis, 2,498 patients (15.8%) underwent PCI for at least one bifurcation lesion. The incidence of the primary endpoint was similar between the bifurcation and nonbifurcation groups (4.7 vs. 4.0%, p = .083). The experimental treatment had no significant effect on the primary endpoint according to the presence/absence of a bifurcation lesion (bifurcation: hazard ratio [HR]: 0.74, 95% confidence interval [CI]: 0.51-1.07; nonbifurcation: HR: 0.90, 95% CI: 0.76-1.07, p for interaction = .343), but was associated with significant reduction in definite or probable stent thrombosis (p for interaction = .022) and significant excess of stroke (p for interaction = .018) when compared with the reference treatment. CONCLUSIONS: After PCI for bifurcation lesions using 1-month of DAPT followed by ticagrelor monotherapy for 23 months did not demonstrate explicit benefit regarding all-cause death or new Q-wave MI as in the overall trial.

Clinical Implication of Quantitative Flow Ratio After Percutaneous Coronary Intervention for 3-Vessel Disease.

OBJECTIVES: The aim of this study was to investigate the impact of post-percutaneous coronary intervention (PCI) quantitative flow ratio (QFR) on clinical outcomes in patients with de novo 3-vessel disease (3VD) treated with contemporary PCI. BACKGROUND: The clinical impact of post-PCI QFR in patients treated with state-of-the-art PCI for de novo 3VD is undetermined. METHODS: All vessels treated in the SYNTAX (SYNergy between percutaneous coronary intervention with TAXus and cardiac surgery) II trial were retrospectively screened and analyzed for post-PCI QFR. The primary endpoint of this substudy was vessel-oriented composite endpoint (VOCE) at 2 years, defined as the composite of vessel-related cardiac death, vessel-related myocardial infarction, and target vessel revascularization. The receiver-operating characteristic curve was used to calculate the optimal cutoff value of post-PCI QFR for predicting 2-year VOCE. All the analyzable vessels were stratified on the basis of the optimal cutoff value. RESULTS: A total of 968 vessels treated with PCI were screened. Post-PCI QFR was analyzable in 771 (79.6%) vessels. A total of 52 (6.7%) VOCEs occurred at 2 years. The mean value of post-PCI QFR was 0.91 ± 0.07. The diagnostic performance of post-PCI QFR to predict 2-year VOCE was moderate (area under the curve: 0.702; 95% confidence interval: 0.633 to 0.772), with the optimal cutoff value of post-PCI QFR for predicting 2-year VOCE 0.91 (sensitivity 0.652, specificity 0.635). The incidence of 2-year VOCE in the vessels with post-PCI QFR <0.91 (n = 284) was significantly higher compared with vessels with post-PCI QFR ≥0.91 (n = 487) (12.0% vs. 3.7%; hazard ratio: 3.37; 95% confidence interval: 1.91 to 5.97; p < 0.001). CONCLUSIONS: A higher post-PCI QFR value is associated with improved vessel-related clinical outcomes in state-of-the art PCI practice for de novo 3VD. Achieving a post-PCI QFR value ≥0.91 in all treated vessels should be a target when treating de novo 3VD. These findings require confirmation in future prospective trials.

Impact of long-term ticagrelor monotherapy following 1-month dual antiplatelet therapy in patients who underwent complex percutaneous coronary intervention: insights from the Global Leaders trial.

AIMS: To evaluate the impact of an experimental strategy [23-month ticagrelor monotherapy following 1-month dual antiplatelet therapy (DAPT)] vs. a reference regimen (12-month aspirin monotherapy following 12-month DAPT) after complex percutaneous coronary intervention (PCI). METHODS AND RESULTS: In the present post hoc analysis of the Global Leaders trial, the primary endpoint [composite of all-cause death or new Q-wave myocardial infarction (MI)] at 2 years was assessed in patients with complex PCI, which includes at least one of the following characteristics: multivessel PCI, ≥3 stents implanted, ≥3 lesions treated, bifurcation PCI with ≥2 stents, or total stent length >60 mm. In addition, patient-oriented composite endpoint (POCE) (composite of all-cause death, any stroke, any MI, or any revascularization) and net adverse clinical events (NACE) [composite of POCE or Bleeding Academic Research Consortium (BARC) Type 3 or 5 bleeding] were explored. Among 15 450 patients included in this analysis, 4570 who underwent complex PCI had a higher risk of ischaemic and bleeding events. In patients with complex PCI, the experimental strategy significantly reduced risks of the primary endpoint [hazard ratio (HR): 0.64, 95% confidence interval (CI): 0.48-0.85] and POCE (HR: 0.80, 95% CI: 0.69-0.93), but not in those with non-complex PCI (Pinteraction = 0.015 and 0.017, respectively). The risk of BARC Type 3 or 5 bleeding was comparable (HR: 0.97, 95% CI: 0.67-1.40), resulting in a significant risk reduction in NACE (HR: 0.80, 95% CI: 0.69-0.92; Pinteraction = 0.011). CONCLUSION: Ticagrelor monotherapy following 1-month DAPT could provide a net clinical benefit for patients with complex PCI. However, in view of the overall neutral results of the trial, these findings of a post hoc analysis should be considered as hypothesis generating.

Contemporary Outcomes Following Coronary Artery Bypass Graft Surgery for Left Main Disease.

BACKGROUND: Although results of percutaneous coronary intervention (PCI) have been steadily improving, whether surgical outcomes have improved over time is not fully elucidated. OBJECTIVES: This study sought to compare the current outcomes of patients undergoing coronary artery bypass grafting (CABG) with prior surgical results, in the context of randomized trials including the left main (LM) coronary artery stem. METHODS: The authors performed a propensity-matched analysis of patients randomized to CABG in the SYNTAX (Synergy Between PCI With Taxus and Cardiac Surgery) (enrollment period 2005 to 2007) and EXCEL (Evaluation of XIENCE Versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization) (enrollment period 2010 to 2014) trials. All patients had left main (LM) disease with or without multivessel disease. Adjustment was based on 15 clinical and angiographic variables, including anatomic SYNTAX score, with a 2:1 ratio for the EXCEL and SYNTAX trials, collectively analyzing 909 subjects (n = 580 and n = 329, respectively). The primary endpoint was the composite of all-cause death, myocardial infarction (MI), stroke, or ischemia-driven revascularization at 3 years. RESULTS: Baseline characteristics, anatomic SYNTAX score, number and types of grafts, and duration of hospitalization for the procedures were similar in both groups. CABG procedures in the EXCEL compared with the SYNTAX trial were more often off-pump (29.6% vs. 15.4%; p < 0.001), and guideline-directed medical therapies were used more frequently in the EXCEL surgical cohort. The primary endpoint occurred in 14.0% and 20.9% (p = 0.008) of patients in the EXCEL and SYNTAX trials, respectively. With the exception of MI (4.1% vs. 3.7%), all nonhierarchical events tended to contribute to the improved outcomes in the more recent trial: all-cause death (5.5% vs. 8.5%), stroke (3.1% vs. 5.1%), and ischemia-driven revascularization (7.1% vs. 9.4%) in the EXCEL and SYNTAX trials, respectively. CONCLUSIONS: Over a 5- to 7-year period, significant improvement in event-free survival after surgical revascularization for LM disease at 3 years was noted between the SYNTAX and EXCEL trials, consistent with improving results with cardiac surgery over time. (Synergy Between PCI With Taxus and Cardiac Surgery [SYNTAX]; NCT00114972; Evaluation of XIENCE Versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization [EXCEL]; NCT01205776).

Predictive ability of ACEF and ACEF II score in patients undergoing percutaneous coronary intervention in the GLOBAL LEADERS study.

BACKGROUND: ACEF score has been shown to have predictive ability in the patients undergoing percutaneous coronary intervention (PCI). The ACEF II score has recently been developed to predict short-term mortality after cardiac surgery. We compared the predictive ability of the ACEF and ACEF II scores to predict mortality after PCI in the all-comers population. METHODS: The ACEF and ACEF II scores were calculated in 15,968 patients enrolled in the GLOBAL LEADERS study. Discrimination and calibration were assessed for outcomes after PCI. Recalibration of the regression model by updating the intercept and slope were performed to adjust the original ACEF model to the PCI setting. In a stratified approach, patients were divided into quintiles according to the score. Outcomes were compared between quintiles. RESULTS: The ACEF and ACEF II score were available in 14,941 and 14,355 patients respectively. Discrimination for 30-day all-cause mortality was acceptable for both scores (C-statistic ACEF 0.75 and ACEF II 0.77). For 2-year all-cause mortality, the discrimination of ACEF score was acceptable (C-statistic 0.72) while the discrimination of ACEF II score was moderate (C-statistic 0.69). Both scores identified patients at high risk of mortality but overestimated all-cause mortality at 30 days in all quintiles. After recalibration, agreement between predicted and observed 30-day all-cause mortality in both scores are close to the identity line. CONCLUSIONS: The ACEF II model did not improve the predictive ability of the ACEF score. Recalibrated ACEF model can be used to estimated all-cause mortality rate at 30 days after PCI.

Angiography-Derived Fractional Flow Reserve in the SYNTAX II Trial: Feasibility, Diagnostic Performance of Quantitative Flow Ratio, and Clinical Prognostic Value of Functional SYNTAX Score Derived From Quantitative Flow Ratio in Patients With 3-Vessel Disease.

OBJECTIVES: The aims of the present study were to investigate the applicability of quantitative flow ratio (QFR) in patients with 3-vessel disease and to demonstrate the impact of functional SYNTAX (Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery) score derived from QFR (fSSQFR) on clinical outcomes. BACKGROUND: The applicability of QFR in patients with 3-vessel disease and the feasibility of fSSQFR have not yet been investigated. METHODS: All lesions interrogated using instantaneous wave-free ratio and/or fractional flow reserve in the SYNTAX II trial were retrospectively screened and analyzed for QFR. The diagnostic performance of QFR was investigated using hybrid wire-derived pressure assessment (instantaneous wave-free ratio and fractional flow reserve), used in the trial as a reference. Patients with analyzable QFR in 3 vessels were stratified according to fSSQFR to evaluate its clinical prognostic value on the basis of 2-year patient-oriented composite endpoint. RESULTS: QFRs were analyzable in 71.0% of lesions (836 lesions). The diagnostic performance of QFR to predict binary wire-based ischemia was substantial (area under the curve 0.81, accuracy 73.8%), with a positive predictive value of 85.9%. Independent predictors of diagnostic discordance were lesions in side branches, involvement of bifurcation or trifurcation, and small vessel. According to the 2-year patient-oriented composite endpoint, fSSQFR reclassified 26.1% of the patients (36 of 138) in the high- to intermediate-risk group into the low-risk group appropriately (net reclassification improvement 0.32; p < 0.001). The area under the curve for fSSQFR to predict the 2-year patient-oriented composite endpoint was higher than that of the classic anatomic SYNTAX score (0.68 vs. 0.56; p = 0.002). CONCLUSIONS: QFR demonstrated substantial applicability in patients with 3-vessel disease. The fSSQFR has the potential to further refine prognostic risk estimation compared with the classic anatomic SYNTAX score.

Ticagrelor plus aspirin for 1 month, followed by ticagrelor monotherapy for 23 months vs aspirin plus clopidogrel or ticagrelor for 12 months, followed by aspirin monotherapy for 12 months after implantation of a drug-eluting stent: a multicentre, open-label, randomised superiority trial.

BACKGROUND: We hypothesised that ticagrelor, in combination with aspirin for 1 month, followed by ticagrelor alone, improves outcomes after percutaneous coronary intervention compared with standard antiplatelet regimens. METHODS: GLOBAL LEADERS was a randomised, open-label superiority trial at 130 sites in 18 countries. Patients undergoing percutaneous coronary intervention with a biolimus A9-eluting stent for stable coronary artery disease or acute coronary syndromes were randomly assigned (1:1) to 75-100 mg aspirin daily plus 90 mg ticagrelor twice daily for 1 month, followed by 23 months of ticagrelor monotherapy, or standard dual antiplatelet therapy with 75-100 mg aspirin daily plus either 75 mg clopidogrel daily (for patients with stable coronary artery disease) or 90 mg ticagrelor twice daily (for patients with acute coronary syndromes) for 12 months, followed by aspirin monotherapy for 12 months. Randomisation was concealed, stratified by centre and clinical presentation (stable coronary artery disease vs acute coronary syndrome), and blocked, with randomly varied block sizes of two and four. The primary endpoint at 2 years was a composite of all-cause mortality or non-fatal centrally adjudicated new Q-wave myocardial infarction as assessed by a core lab in a blinded manner. The key secondary safety endpoint was site-reported bleeding assessed according to the Bleeding Academic Research Consortium criteria (grade 3 or 5). Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01813435, and is closed to new participants, with follow-up completed. FINDINGS: Between July 1, 2013, and Nov 9, 2015, 15 968 participants were randomly assigned, 7980 to the experimental group and 7988 to the control group. At 2 years, 304 (3·81%) participants in the experimental group had died or had a non-fatal centrally adjudicated new Q-wave myocardial infarction, compared with 349 (4·37%) participants in the control group (rate ratio 0·87 [95% CI 0·75-1·01]; p=0·073]). There was no evidence for a difference in treatment effects for the primary endpoint across prespecified subgroups of acute coronary syndromes and stable coronary artery disease (p=0·93). Grade 3 or 5 bleeding occurred in 163 participants in the experimental group and 169 in the control group (2·04% vs 2·12%; rate ratio 0·97 [95% CI 0·78-1·20]; p=0·77). INTERPRETATION: Ticagrelor in combination with aspirin for 1 month followed by ticagrelor alone for 23 months was not superior to 12 months of standard dual antiplatelet therapy followed by 12 months of aspirin alone in the prevention of all-cause mortality or new Q-wave myocardial infarction 2 years after percutaneous coronary intervention. FUNDING: AstraZeneca, Biosensors, and The Medicines Company.

Fractional Flow Reserve Derived From Computed Tomographic Angiography in Patients With Multivessel CAD.

BACKGROUND: The functional SYNTAX score (FSS) has been shown to improve the discrimination for major adverse cardiac events compared with the anatomic SYNTAX score (SS) while reducing interobserver variability. However, evidence supporting the noninvasive FSS in patients with multivessel coronary artery disease (CAD) is scarce. OBJECTIVES: The purpose of this study was to assess the feasibility of and validate the noninvasive FSS derived from coronary computed tomography angiography (CTA) with fractional flow reserve (FFRCT) in patients with 3-vessel CAD. METHODS: The CTA-SS was calculated in patients with 3-vessel CAD included in the SYNTAX II (SYNergy between percutaneous coronary intervention with TAXus and cardiac surgery II) study. The noninvasive FSS was determined by including only ischemia-producing lesions (FFRCT ≤0.80). SS derived from different imaging modalities were compared using the Bland-Altman and Passing-Bablok method, and the agreement on the SS tertiles was investigated with Cohen's Kappa. The risk reclassification was compared between the noninvasive and invasive physiological assessment, and the diagnostic accuracy of FFRCT was assessed by the area under the receiver-operating characteristic curve using instantaneous wave-free ratio as a reference. RESULTS: The CTA-SS was feasible in 86% of patients (66 of 77), whereas the noninvasive FSS was feasible in 80% (53 of 66). The anatomic SS was overestimated by CTA compared with conventional angiography (27.6 ± 6.4 vs. 25.3 ± 6.9; p < 0.0001) whereas the calculation of the FSS yielded similar results between the noninvasive and invasive imaging modalities (21.6 ± 7.8 vs. 21.2 ± 8.8; p = 0.589). The noninvasive FSS reclassified 30% of patients from the high- and intermediate-SS tertiles to the low-risk tertile, whereas invasive FSS reclassified 23% of patients from the high- and intermediate-SS tertiles to the low-risk tertile. The agreement on the classic SS tertiles based on Kappa statistics was slight for the anatomic SS (Kappa = 0.19) and fair for the FSS (Kappa = 0.32). The diagnostic accuracy of FFRCT to detect functional significant stenosis based on an instantaneous wave-free ratio ≤0.89 revealed an area under the receiver-operating characteristics curve of 0.85 (95% CI: 0.79 to 0.90) with a sensitivity of 95% (95% CI: 89% to 98%), specificity of 61% (95% CI: 48% to 73%), positive predictive value of 81% (95% CI: 76% to 86%), and negative predictive value of 87% (95% CI: 74% to 94%). CONCLUSIONS: Calculation of the noninvasive FSS is feasible and yielded similar results to those obtained with invasive pressure-wire assessment. The agreement on the SYNTAX score tertile classification improved with the inclusion of the functional component from slight to fair agreement. FFRCT has good accuracy in detecting functionally significant lesions in patients with 3-vessel CAD. (A Trial to Evaluate a New Strategy in the Functional Assessment of 3-Vessel Disease Using SYNTAX II Score in Patients Treated With PCI; NCT02015832).