Updated CRUSADE score to predict in-hospital bleeding: External validation in the Thai percutaneous coronary intervention registry.

BACKGROUND: The Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes with Early Implementation of the ACC/AHA Guidelines (CRUSADE) score has been recommended to predict in-hospital bleeding risk in non-ST segment elevation myocardial infarction (NSTEMI) patients. The evaluation of the CRUSADE risk score in Asian patients undergoing contemporary percutaneous coronary intervention (PCI) for NSTEMI is necessary. AIMS: We aimed to validate and update the CRUSADE score to predict in-hospital major bleeding in NSTEMI patients treated with PCI. METHOD: The Thai PCI registry is a large, prospective, multicenter PCI registry in Thailand enrolling patients between May 2018 and August 2019. The CRUSADE score was calculated based on 8 predictors including sex, diabetes, prior vascular disease (PVD), congestive heart failure (CHF), creatinine clearance (CrCl), hematocrit, systolic blood pressure, and heart rate (HR). The score was fitted to in-hospital major bleeding using the logistic regression. The original score was revised and updated for simplification. RESULTS: Of 19,701 patients in the Thai PCI registry, 5976 patients presented with NSTEMI. The CRUSADE score was calculated in 5882 patients who had all variables of the score available. Thirty-five percent were female, with a median age of 65.1 years. The proportion of diabetes, PVD, and CHF was 46%, 7.9%, and 11.2%, respectively. The original and revised models of the CRUSADE risk score had C-statistics of 0.817 (95% CI: 0.762-0.871) and 0.839 (95% CI: 0.789-0.889) respectively. The simplified CRUSADE score which contained only four variables (hematocrit, CrCl, HR, and CHF), had C-statistics of 0.837 (0.787-0.886). The calibration of the recalibrated, revised, and simplified model was optimal. CONCLUSIONS: The full and simplified CRUSADE scores performed well in NSTEMI treated with PCI in Thai population.

Clinical outcomes of patients with atrial fibrillation in relation to multimorbidity status changes over time and the impact of ABC pathway compliance: a nationwide cohort study.

Patients with atrial fibrillation (AF) commonly have associated comorbidities. The primary aim was to determine the effect of increasing numbers of comorbidity on clinical outcomes. The secondary aims were (1) the association of comorbidities with oral anticoagulants (OAC) discontinuation, and quality control, (2) the impact of holistic care based on the ABC pathway on clinical outcomes. The primary outcome was the composite of all-cause death, ischemic stroke/systemic embolism, major bleeding, and heart failure. A total of 3405 patients were enrolled; mean age 67.8 ± 11.3 years, 41.8% female. Compared to low comorbidity group [n = 897 (26.3%)], hazard ratios (HR) and 95% confidence intervals (CI) for the composite outcome in the high [n = 929 (27.3%)] and moderate comorbidity [n = 1579 (46.4%)] groups were 5.40 (4.20-6.94) and 2.54 (1.97-3.27), respectively. ABC pathway adherence was associated with reduction of the composite outcome overall (HR 0.63; 0.54-0.74). High comorbidity adversely impacted on OAC use, OAC discontinuation, and quality of warfarin control. If quality of anticoagulation control was included as part of the ABC pathway adherence, the reduction in composite outcome risk was greater (HR 0.46; 0.36-0.58). During 3-year follow-up, 33.9% changed from low- to the moderate-high comorbidity groups and 22.3% changed from moderate- to the high comorbidity group. In conclusion, comorbidity burden in AF patients is an important determinant of clinical outcomes, and changed over time. OAC use, OAC discontinuation, and quality of OAC control were impacted by comorbidity burden. ABC pathway adherence was associated with a reduced risk of adverse clinical outcomes.

Comparative validation of HAS-BLED, GARFIELD-AF and ORBIT bleeding risk scores in Asian people with atrial fibrillation treated with oral anticoagulant: A report from the COOL-AF registry.

AIMS: Comparative data between the HAS-BLED, GARFIELD-AF and ORBIT score are limited in anticoagulated Asian patients with atrial fibrillation (AF). We compared the performance of the 3 scores in a nationwide registry. METHODS: AF patients treated with oral anticoagulants in the COOL-AF registry were studied. We fitted the variables of the HAS-BLED, GARFIELD-AF and ORBIT score to major bleeding in Cox model. We explored a modified HAS-BLED by addition of sex and body weight. Discrimination, calibration, net reclassification index (NRI) and decision curve analysis were used to compare the performance of the 3 models. RESULTS: Of 3402 patients in the registry, 2568 patients who received oral anticoagulant at baseline were studied. Majority of patients (91.1%) received warfarin. The rate of major bleeding was 2.11 per 100 person-years. The C-statistics of the GARFIELD-AF, HAS-BLED, modified HAS-BLED and ORBIT score were 0.65 (95% confidence interval [CI] 0.63-0.67), 0.66 (95%CI 0.64-0.68), 0.69 (95%CI 0.67-0.71) and 0.64 (95%CI 0.62-0.66) respectively. There was good agreement between predicted and observed bleeding in the deciles of HAS-BLED and GARFIELD-AF scores, while the modified HAS-BLED score and ORBIT score overestimated the risk in the last decile. The modified HAS-BLED score had superior NRI than the HAS-BLED score (26.9%, 95%CI 9.7%-42.2%) and the ORBIT score (31.9%, 95%CI 9.0-53.6%). The NRI between the modified HAS-BLED and GARFIELD-AF score was similar. The net benefit curve of the 4 models were overlapping among different thresholds. CONCLUSIONS: The clinical utility for bleeding prediction of GARFIELD-AF, HAS-BLED, modified HAS-BLED and ORBIT scores were similar in anticoagulated Asian patients with AF participating in the COOL-AF registry. We found no advantage of the ORBIT over HAS-BLED score for bleeding risk prediction, even in direct oral anticoagulant users.

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.

Net clinical benefit of oral anticoagulants in Asian patients with atrial fibrillation based on a CHA2DS2-VASc score.

BACKGROUND: This study was conducted to assess the net clinical benefit (NCB) for oral anticoagulant (OAC) in atrial fibrillation (AF) patients according to the CHA2DS2-VASc score. METHODS: Patients with AF were prospectively recruited in the COOL AF Thailand registry from 2014 to 2017. The incidence rate of thromboembolic (TE) events and major bleeding (MB) was calculated. Cox proportional hazards model was used to compare the TE and MB rate in patients with and without OACs in CHA2DS2-VASc score of 0-1 and ≥ 2, respectively. The survival analysis was performed based on CHA2DS2-VASc score. The NCB of OACs was defined as the TE rate prevented minus the MB rate increased multiplied by a weighting factor. RESULTS: A total of 3,402 AF patients were recruited. An average age of patients was 67.38 ± 11.27 years. Compared to non-anticoagulated patients, the Kaplan Meier curve showed anticoagulated patients with CHA2DS2-VASc score of 2 or more had the lower thromboembolic events with statistical significance (p = 0.043) and the higher MB events with statistical significance (p = 0.018). In overall AF patients, there were positive NCB in warfarin patients with CHA2DS2-VASc score of 3 or more while there were positive NCB in DOACs patients regardless of CHA2DS2-VASc score. Females with CHA2DS2-VASc score of 3 or more had a positive NCB regardless of OACs type. Good anticoagulation control (TTR ≥65%) improved an NCB in males with CHA2DS2-VASc score of 3 or more. CONCLUSIONS: AF patients with CHA2DS2-VASc score of 3 or more regardless warfarin or DOACs had a positive NCB. The NCB of OACs was more positive for DOACs compared to warfarin and for females compared to males.

Utility of the dual antiplatelet therapy score to guide antiplatelet therapy: A systematic review and meta-analysis.

BACKGROUND: The dual antiplatelet therapy (DAPT) score, one of the first prediction tools to attempt to uncouple bleeding and ischemic risk following percutaneous coronary intervention, can help guide antiplatelet duration after coronary intervention. Evaluating the generalizability of the score is important to understand its utility in clinical practice. METHODS: We conducted a systematic review and meta-analysis of studies that validated the DAPT score. A random effect meta-analysis was performed of ischemic and bleeding risk based on DAPT score. A secondary analysis assessed the risk of longer versus shorter P2Y12 inhibitor duration on ischemic and bleeding risk in randomized controlled trials of DAPT duration. RESULTS: We identified 10 patient cohorts involving 88,563 patients. Compared with a low DAPT score, a high DAPT score was associated with increased ischemic risk (RR: 1.62, 95% CI: 1.41-1.87) and reduced bleeding risk (RR: 0.80, 95% CI: 0.70-0.92). In three randomized trials of DAPT duration that contained information on the DAPT score, the relative risk of net adverse clinical events (combined ischemic and bleeding events) with longer duration of DAPT was 1.56 (95% CI: 0.77-3.19) for low DAPT score patients, and 0.86 (95% CI: 0.61-1.21) for high DAPT score patients (pinteraction = .14). CONCLUSIONS: In this large meta-analysis, the DAPT score consistently stratified bleeding and ischemic risk in opposing directions across several different study populations. More evaluation is needed to understand if the effect of longer DAPT duration on NACE is modified by the DAPT score in current practice.

Predicting 2-year all-cause mortality after contemporary PCI: Updating the logistic clinical SYNTAX score.

AIMS: We aimed to update the logistic clinical SYNTAX score to predict 2 year all-cause mortality after contemporary percutaneous coronary intervention (PCI). METHODS AND RESULTS: We analyzed 15,883 patients in the GLOBAL LEADERS study who underwent PCI. The logistic clinical SYNTAX model was updated after imputing missing values by refitting the original model (refitted original model) and fitting an extended new model (new model, with, selection based on the Akaike Information Criterion). External validation was performed in 10,100 patients having PCI at Fu Wai hospital. Chronic obstructive pulmonary disease, prior stroke, current smoker, hemoglobin level, and white blood cell count were identified as additional independent predictors of 2 year all-cause mortality and included into the new model. The c-indexes of the original, refitted original and the new model in the derivation cohort were 0.74 (95% CI 0.72-0.76), 0.75 (95% CI 0.73-0.77), and 0.78 (95% CI 0.76-0.80), respectively. The c-index of the new model was lower in the validation cohort than in the derivation cohort, but still showed improved discriminative ability of the newly developed model (0.72; 95% CI 0.67-0.77) compared to the refitted original model (0.69; 95% CI 0.64-0.74). The models overestimated the observed 2 year all-cause mortality of 1.11% in the Chinese external validation cohort by 0.54 percentage points, indicating the need for calibration of the model to the Chinese patient population. CONCLUSIONS: The new model of the logistic clinical SYNTAX score better predicts 2 year all-cause mortality after PCI than the original model. The new model could guide clinical decision making by risk stratifying patients undergoing PCI.

Two years clinical outcomes with the state-of-the-art PCI for the treatment of bifurcation lesions: A sub-analysis of the SYNTAX II study.

BACKGROUND: Bifurcation PCI is associated with a lower rate of procedural success, especially in multivessel disease patients. We aimed to determine the impact of bifurcation treatment on 2-years clinical outcomes when a state-of-the-art PCI strategy (heart team decision-making using the SYNTAX score II, physiology guided coronary stenosis assessment, thin strut bioresorbable polymer drug-eluting stent, and intravascular ultrasound guidance) is followed. METHODS: Three-vessel disease patients enrolled in the SYNTAX II trial (n = 454) were categorized in patients with (a) ≥1 treated bifurcation (n = 126), and (b) without bifurcation (n = 281). The primary endpoint was the occurrence of major adverse cardio and cerebrovascular events (MACCE-a composite of all-cause death, stroke, any myocardial infarction, or any revascularization) at 2 years. Secondary endpoints were the occurrence of target lesion failure (TLF) defined as cardiac death, target-vessel myocardial infarction and ischemia-driven target lesion revascularization, and the individual components of the composite primary endpoint, as well as stent thrombosis. RESULTS: A total of 145 bifurcation were treated in 126 patients. At 2 years, MACCE occurred in 75/407 patients (20.7% for bifurcation versus 17.5% for nonbifurcation, hazard ratio [HR] of 1.28, CI95% 0.78-2.08, p = .32). TLF presented a trend toward higher occurrence in bifurcation (16.8% vs. 10.8%, HR 1.75, CI95% 0.99-3.09, p = .053). Definite stent thrombosis did not differ at 2-year between groups (0.8% for the bifurcation vs. 0.7% for the nonbifurcation, p = .92). CONCLUSION: Bifurcation treatment in patients with three-vessel disease undergoing state-of-the-art PCI had similar event rate of MACCE but was associated with a trend toward higher incidence of TLF compared with nonbifurcation lesions.

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.

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 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.

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.

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.

Application of the MADS classification system in a "mega mammoth" stent trial: Feasibility and preliminary clinical implications.

OBJECTIVES AND BACKGROUND: We attempted to test the feasibility of application of the MADS classification system in the largest stent trial to date and evaluate the preliminary clinical implications of this approach. METHODS: In the randomized GLOBAL LEADERS trial, testing two different antiplatelet strategies in patients undergoing PCI with bivalirudin and biolimus-eluting stents, the e-CRF was dedicated to bifurcation treatment according to the MADS classification. Based on this e-CRF, the techniques used for bifurcations treatment in GLOBAL LEADERS were described and compared with two large, all-comer registries of bifurcations treatment (I-BIGIS and COBIS), used as historical controls. RESULTS: Among 15,991 patients enrolled in the trial, 22,921 lesions treated at the index and staged procedure were available for analysis and 2,757 of these lesions were bifurcations and 7 were trifurcation lesions. The e-CRF-based MADS classification was achieved in 2,757 of these lesions (100%). 80.3% of bifurcations were treated using a single stent, 18.9% using 2 stents and 0.7% using 3 stents. Overall, the "main across side first" approach (A) was used in 77.4% with the "side branch first" approach (S) being the second most frequently used technique (10.2%). A single stent was used in the majority of the "A" approach (87.9%). A reduction in the use of 2-stent techniques (from 33.9 to 18.9%) was observed between GLOBAL LEADERS and I-BIGIS. The "A" approach was the most frequently used technique in GLOBAL LEADERS, while in COBIS the "S" strategy was most frequently employed. CONCLUSIONS: Application of the MADS classification through an e-CRF was feasible in the largest stent trial today and provided useful information about the trends observed overtime in the treatment of bifurcation lesions.

Impact of post-procedural minimal stent area on 2-year clinical outcomes in the SYNTAX II trial.

OBJECTIVES: To investigate the impact of minimal stent area (MSA) evaluated by post-procedural intravascular ultrasound (IVUS) on clinical outcomes after contemporary PCI in patients with three-vessel disease (TVD). BACKGROUND: The impact of post-procedural MSA on clinical outcomes has not yet been extensively studied in patients with TVD. METHODS: The SYNTAX II study is a multicenter, all-comers, open-label, single arm study that investigated the impact of a state-of-the-art PCI strategy on clinical outcomes in patients with TVD (454 patients with 1,559 lesions). The relationships between post-procedural MSA and lesion-level outcomes at 2 years were investigated. Clinical events adjudicated per patient by clinical event committee were assessed per lesion. Lesion-oriented composite endpoint (LOCE) was defined as the composite of cardiac death, target-vessel myocardial infarction, and ischemia-driven target lesion revascularization. RESULTS: Eight hundred and nineteen lesions with post-procedural MSA available in 367 patients were included in the analysis. The post-procedural MSA per lesion was divided into terciles (smallest tercile: ≤5.0 mm2 , intermediate tercile: 5.0-6.7 mm2 , and largest tercile: >6.7 mm2 ). LOCE was observed in 16/288 (5.6%), 15/265 (5.7%), and 8/266 (3.0%) (P = 0.266). Target lesion revascularization (TLR) was observed in 16/288(5.6%), 12/265 (4.5%), and 4/266 (1.5%) (P = 0.042). The multivariate analysis demonstrated that smaller post-procedural MSA, as well as creatinine clearance, history of previous stroke, chronic total occlusion, and lesion SYNTAX Score was an independent predictor of TLR. CONCLUSIONS: In the SYNTAX II trial, larger post-procedural MSA was independently associated with the lower rate of TLR at 2 years.

Serial Optical Coherence Tomography at Baseline, 7 Days, and 1, 3, 6 and 12 Months After Bioresorbable Scaffold Implantation in a Growing Porcine Model.

BACKGROUND: Little is known about serial changes in lumen and device dimensions after bioresorbable scaffold implantation in a growing animal model. Methods and Results: ABSORB (n=14) or bare metal stents (ICROS amg [Abbott Vascular, Santa Clara, CA, USA], Winsen-Luhe, Germany; n=15) were implanted in the coronary arteries of domestic swine (a hybrid of Finnish-Norwegian Landrace swine) weighing 30-35 kg. Angiography and optical coherence tomography (OCT) were performed immediately after implantation and repeated at 7 days, 1, 3, 6 and 12 months after the index procedure. One month after implantation, mean lumen area decreased relative to baseline in both groups (relative area change from baseline, -41.4±15.6% for ABSORB vs. -20.9±18.6% for ICROS) while mean device area decreased only in the ABSORB group (relative area change: -11.1±9.4% vs. +0.14±7.95%, respectively). At 12 months, mean lumen area increased relative to baseline in both groups (relative area change from baseline, +55.6±22.4% vs. +32.3±83.6%, respectively) in accordance with the swine growth weighing up to 260-300 kg. Mean device area in the ICROS group remained stable whereas that in the ABSORB group began to increase between 3 and 6 months along with the vessel growth (relative area change: +107.8±25.7% vs. +0.14±7.95%). CONCLUSIONS: In the growing porcine model, ABSORB was associated with greater extent of recoil 1 month after implantation compared with ICROS but demonstrated substantial adaptability to vessel growth in late phase.

Angiographic late lumen loss revisited: impact on long-term target lesion revascularization.

Aim: In current device trials, the values of angiographic late lumen loss (LLL) have become extremely low and the relationship between LLL and clinical endpoints has not been recently re-evaluated. The impact of LLL on target lesion revascularization (TLR) in a patient- and study-level analysis of contemporary coronary devices was investigated. Methods and results: We performed a patient-level meta-analysis of seven randomized controlled trials including 2426 patients treated with first- and second-generation drug-eluting stents (DES) and a study-level meta-analysis of 40 studies including 19 199 patients treated with CE-marked DES. In the patient-level analysis, the probability regression curve showed an exponential relationship between in-stent LLL and 2-year incidence of TLR. The optimal cut-off value of LLL based on Youden's index for 2-year TLR event was 0.50 mm. In the Cox proportional hazard model, LLL >0.50 mm was independently associated with an increased incidence of TLR up to 4 years after angiographic follow-up {adjusted hazard ratio (HR) 6.62 [95% confidence interval (95% CI) 4.67-9.39], P < 0.001}. In the meta-regression analysis of the DES studies, pooled mean value of LLL was as low as 0.23 mm (95% CI 0.20-0.26), and there was a moderate correlation between the 1- and 5-year incidence of TLR and the percentage of the lesions with LLL >0.50 mm (R2 = 0.44, P < 0.001 at 1 year, R2 = 0.40, P < 0.001 at 5 years). Conclusion: An angiographic LLL ≤0.50 mm was not predictive of the incidence of TLR whereas a LLL >0.50 mm was. Low LLL in contemporary device trials may not be a sufficiently discriminating parameter for the comparative evaluation of devices.

Diagnostic performance of angiography-derived fractional flow reserve: a systematic review and Bayesian meta-analysis.

Aims: Pressure-wire assessment of coronary stenosis is considered the invasive reference standard for detection of ischaemia-generating lesions. Recently, methods to estimate the fractional flow reserve (FFR) from conventional angiography without the use of a pressure wire have been developed, and were shown to have an excellent diagnostic accuracy. The present systematic review and meta-analysis aimed at determining the diagnostic performance of angiography-derived FFR for the diagnosis of haemodynamically significant coronary artery disease. Methods and results: A systematic review and meta-analysis of studies assessing the diagnostic performance of angiography-derived FFR systems were performed. The primary outcome of interest was pooled sensitivity and specificity. Thirteen studies comprising 1842 vessels were included in the final analysis. A Bayesian bivariate meta-analysis yielded a pooled sensitivity of 89% (95% credible interval 83-94%), specificity of 90% (95% credible interval 88-92%), positive likelihood ratio (+LR) of 9.3 (95% credible interval 7.3-11.7) and negative likelihood ratio (-LR) of 0.13 (95% credible interval 0.07-0.2). The summary area under the receiver-operating curve was 0.84 (95% credible interval 0.66-0.94). Meta-regression analysis did not find differences between the methods for pressure-drop calculation (computational fluid dynamics vs. mathematical formula), type of analysis (on-line vs. off-line) or software packages. Conclusion: The accuracy of angiography-derived FFR was good to detect haemodynamically significant lesions with pressure-wire measured FFR as a reference. Computational approaches and software packages did not influence the diagnostic accuracy of angiography-derived FFR. A diagnostic strategy trial with angiography-derived FFR evaluating clinical endpoints is warranted.

A comparison of ventricular systolic function indices provided by VolumeView/EV1000™ and left ventricular ejection fraction by echocardiography among septic shock patients.

The aim of this study was to compare the cardiac function index (CFI) and global ejection fraction (GEF) obtained by VolumeView/EV1000™, with the left ventricular ejection fraction (LVEF) by echocardiography in septic shock patients. A prospective observational study was conducted in a medical intensive care unit of a tertiary, teaching university hospital. Thirty-two, mechanical-ventilated septic shock patients were included in this study. We simultaneously measured CFI and GEF with LVEF. The correlation of CFI, GEF along with LVEF and ability of CFI and GEF to predict LVEF ≥ 40, 50 and 60% were evaluated. There were 192 pairs of CFI, GEF and LVEF. CFI was significantly correlated with GEF (r = 0.82, P < 0.0001). A significant correlation was observed between CFI and LVEF (r = 0.56, P < 0.0001) and GEF and LVEF (r = 0.71, P < 0.0001). The CFI and GEF had a good predictive ability for estimating LVEF ≥ 40, 50 and 60%, with an area under receiving operating characteristic (AUC) 0.875-0.934. The CFI ≥ 3/min predicted LVEF ≥ 40% with sensitivity 95.1% and specificity 48.3%. The GEF ≥ 15%, estimated LVEF ≥ 40% with sensitivity 92.6% and specificity 69%. There were 40 thermodilution and LVEF measurements obtained before and after norepinephrine adjustment. Blood pressure as well as the cardiac index were significantly increased, whereas there were no changes in CFI, GEF and LVEF values. Conclusions: Both CFI and GEF obtained by VolumeView/EV1000™, correlated with LVEF, so as to provide a reliable estimation of LV systolic function in septic shock patients.

In-Hospital Outcomes after Rescue Percutaneous Coronary Intervention in Patients with ST Segment Elevation Myocardial Infarction.

Objective: To investigate the outcomes of patients who underwent rescue percutaneous coronary intervention (PCI) for ST segment elevation myocardial infarction (STEMI) after failed thrombolytic therapy. Material and Method: This observational cohort study was conducted between June 1, 2008 and May 31, 2013. Consecutive STEMI patients who underwent either emergency rescue PCI or primary PCI were included. Rescue PCI patients were compared with primary PCI patients. Clinical data including baseline characteristics, angiographic results, periprocedural details, and in-hospital adverse events were reviewed. Results: Three hundred sixteen patients were enrolled, of which 72.5% were male. Mean age of participants was 59.5 years. Rescue PCI and primary PCI was performed in 24 and 292 patients, respectively. Median time from symptom onset to emergency room (ER) arrival was 175 minutes and not statistically different between groups. Thirteen percent of patients were critically ill and in cardiogenic shock upon arrival. Radial artery access was significantly more frequently used in the rescue PCI group. The rescue PCI group had a significantly higher proportion of initial TIMI grade 3 flow than the primary PCI group (rescue PCI 33.3% vs. primary PCI 13.4%, p = 0.042). No significant differences were observed in final TIMI grade 3 between the two groups (rescue PCI 87.5% vs. primary PCI 89.7%, p = 0.77). Rate of platelet glycoprotein IIb/IIIa receptor blocker use was significantly higher in the primary PCI group (41.4% vs. 4.2%, p<0.001). Left ventricular ejection fraction was significantly higher in the rescue PCI group (rescue PCI 57.7% vs. primary PCI 50%, p = 0.013). There were no significant differences between groups for angiographic success rate (rescue PCI 83.3% vs. primary PCI 88.7%, p = 0.229) or procedural success rate (rescue PCI 79.2% vs. primary PCI 85.6%, p = 0.164). Forty-one patients (14%) in primary PCI group and two patients (8.3%) in rescue PCI group died during hospitalization (p = 0.75). Stroke and reinfarction were rare events in this study. Hemorrhagic stroke occurred in one patient in each group. There were no significant differences in major bleeding or major vascular complications between groups. Conclusion: The angiographic outcome and procedural success rates in patients who underwent rescue PCI were not significantly different from rates in patients who underwent primary PCI. Rescue PCI in STEMI can be performed with favorable success rates and in-hospital outcomes and should be considered in patients that experience failure after thrombolytic therapy.