Sirolimus-eluting iron bioresorbable scaffold versus cobalt-chromium everolimus-eluting stents in patients with coronary artery disease: Rationale and design of the IRONMAN-II trial.

BACKGROUND: The previous first-in-human study established the preliminary safety and effectiveness of the novel thin-strut iron bioresorbable scaffold (IBS). The current study aims to directly compare the imaging and physiological efficacy, and clinical outcomes of IBS with contemporary metallic drug-eluting stents (DES). METHODS: A total of 518 patients were randomly allocated to treatment with IBS (257 patients) or metallic DES (261 patients) from 36 centers in China. The study is powered to test noninferiority of the IBS compared with the metallic everolimus-eluting stent in terms of the primary endpoint of in-segment late lumen loss at 2 years, and major secondary endpoints including 2-year quantitative flow ratio and cross-sectional mean flow area measured by optical coherence tomography (OCT) (limited to the OCT subgroup, 25 patients in each group). CONCLUSION: This will be the first powered randomized trial investigating the safety and efficacy of the novel thin-strut IBS compared to a contemporary metallic DES. The findings will provide valuable evidence for future research of this kind and the application of metallic bioresorbable scaffolds.

Diagnostic performance of ultrasonic flow ratio versus quantitative flow ratio for assessment of coronary stenosis.

BACKGROUND: Ultrasonic flow ratio (UFR) is a novel intravascular ultrasound (IVUS)-derived modality for fast computation of fractional flow reserve (FFR) without pressure wires and adenosine. AIMS: This study was sought to compare the diagnostic performance of UFR and quantitative flow ratio (QFR), using FFR as the reference standard. METHODS: This is a retrospective study enrolling consecutive patients with intermediate coronary artery lesions (diameter stenosis of 30%-90% by visual estimation) for IVUS and FFR measurement. UFR and QFR were performed offline in a core-lab by independent analysts blinded to FFR. RESULTS: From December 2022 to May 2023, a total of 78 eligible patients were enrolled. IVUS and FFR measurements were successfully conducted in 104 vessels, finally 98 vessels with both FFR, UFR and QFR evaluation were analyzed. Mean FFR was 0.79 ± 0.12. UFR showed a strong correlation with FFR similar to QFR (r = 0.83 vs. 0.82, p = 0.795). Diagnostic accuracy of UFR was non-inferior to QFR (94% [89%-97%] versus 90% [84%-94%], p = 0.113). Sensitivity and specificity in identifying hemodynamically significant stenosis were comparable between UFR and QFR (sensitivity: 89% [79%-96%] versus 85% [74%-92%], p = 0.453; specificity: 97% [91%-99%] versus 95% [88%-99%], p = 0.625). The area under curve for UFR was 0.95 [0.90-0.98], non-inferior to QFR (difference = 0.021, p = 0.293), and significantly higher than minimum lumen area (MLA; difference = 0.13, p < 0.001). Diagnostic accuracy of UFR and QFR was not statically different in bifurcation nor non-bifurcation lesions. CONCLUSIONS: UFR showed excellent concordance with FFR, non-inferior to QFR, superior to MLA. UFR provides a potentiality for the integration of physiological assessment and intravascular imaging in clinical practice.

Impact of Preoperative Quantitative Flow Ratio of the Left Anterior Descending Artery on Internal Mammary Artery Graft Patency and Midterm Patient Outcomes After Coronary Artery Bypass Grafting.

Background In coronary artery bypass grafting, grafting a target vessel with nonsignificant stenosis increases the risk of graft failure. The present study aims to investigate the impact of preoperative quantitative flow ratio (QFR), a novel functional assessment of the coronary artery, on internal mammary artery graft failure rate and midterm patient outcomes. Methods and Results Between January 2016 and January 2020, we retrospectively included 419 patients who underwent coronary artery bypass grafting who had received preoperative angiography and postoperative coronary computed tomographic angiography in our center. QFR of the left anterior descending (LAD) artery was computed based on preoperative angiograms. The primary end point was the failure of the graft on the LAD artery assessed by coronary computed tomographic angiography at 1 year, and the secondary end point was major adverse cardiac and cerebrovascular events including death from any cause, myocardial infarction, stroke, or repeat revascularization. Grafts on functionally nonsignificant LAD arteries (QFR >0.80) had a significantly higher failure rate than those on functionally significant LAD arteries (31.4% versus 7.2%, P<0.001). QFR outperforms degree of stenosis in discriminating graft failure (C statistic, 0.76 versus 0.58). Clinical follow-up (3.6 years, interquartile range [3.3-4.1]) was accomplished in 405 patients, and the rate of major adverse cardiac and cerebrovascular events was significantly higher among patients with functionally nonsignificant LAD arteries (10.1% versus 4.2%; adjusted hazard ratio, 3.08 [95% CI, 1.18-8.06]; P=0.022). Conclusions In patients receiving internal mammary artery to LAD artery coronary artery bypass grafting, preoperative QFR of the LAD artery of >0.80 was associated with a higher graft failure rate at 1 year and worse patient outcomes at the 3.6-year follow-up.

Outcomes of quantitative flow ratio-based functional incomplete revascularization after coronary artery bypass grafting surgery.

OBJECTIVE: Quantitative flow ratio is a novel functional assessment tool of coronary diseases. Whether quantitative flow ratio could improve the outcomes of coronary artery bypass grafting is undetermined. This study aimed to investigate the association between the quantitative flow ratio based functional incomplete revascularization and the outcomes after coronary artery bypass grafting surgery. METHODS: The quantitative flow ratio assessment was retrospectively performed in patients undergoing coronary artery bypass grafting surgery in the PATENCY trial. The anatomic complete revascularization denoted revascularizing each territory with stenosis greater than 50% evaluated by angiography. The functional complete revascularization was defined as grafting all vessels with a quantitative flow ratio 0.80 or less. The primary end point was the 12-month composite major adverse cardiac or cerebral vascular events. RESULTS: A total of 2024 patients with available quantitative flow ratio values were included. Functional complete revascularization was achieved in 1846 patients (91.2%), and 1600 received anatomic complete revascularization (79.1%). Both the functional incomplete revascularization and anatomic incomplete revascularization groups were associated with significantly increased risks of 12-month major adverse cardiac or cerebral vascular events (functional: hazard ratio, 2.91; 95% confidence interval, 1.56 to 5.43; P = .001; anatomic: hazard ratio, 2.82; 95% confidence interval, 1.54 to 5.16; P = .001). Additionally, for the subgroup of patients (n = 246) receiving anatomic incomplete revascularization but judged as functional complete revascularization by quantitative flow ratio, the risk of the 12-month major adverse cardiac or cerebral vascular events was not significantly increased (adjusted hazard ratio, 1.36; 95% confidence interval, 0.71-2.60; P = .35). CONCLUSIONS: Both the functional incomplete revascularization and anatomic incomplete revascularization were associated with increased risks of 12-month major adverse cardiac or cerebral vascular events after coronary artery bypass grafting surgery. The quantitative flow ratio can serve as a supplementary tool for the decision-making of surgical revascularization.

Quantitative flow ratio and graft outcomes of coronary artery bypass grafting surgery: A retrospective study.

OBJECTIVE: Quantitative flow ratio (QFR) is a novel noninvasive tool for the functional assessment of coronary stenosis. Whether or not QFR could predict graft outcomes after coronary artery bypass grafting procedure is unknown. This study aimed to investigate the association of QFR value with graft outcomes after coronary artery bypass grafting surgery. METHODS: The QFR values were retrospectively obtained from patients receiving coronary artery bypass grafting surgery from 2017 to 2019 in the Graft Patency Between No-Touch Vein Harvesting Technique and Conventional Approach in Coronary Artery Bypass Graft Surgery (PATENCY) trial. QFR calculation was conducted in eligible coronary arteries, defined as those with ≥50% stenosis and a diameter ≥1.5 mm. A threshold of QFR ≤0.80 was considered functionally significant stenosis. The primary outcome was graft occlusion at 12 months evaluated by computed tomography angiography. RESULTS: Two thousand twenty-four patients with 7432 grafts (2307 arterial grafts and 5125 vein grafts) were included. For the arterial grafts, the risk of 12-month occlusion was significantly increased in the QFR >0.80 group than in the QFR ≤0.80 group (7.1% vs 2.6%; P = .001; unadjusted model: odds ratio, 3.08; 95% CI, 1.65-5.75; fully adjusted model: odds ratio, 2.67; 95% CI, 1.44-4.97). No significant association was observed in the vein grafts (4.6% vs 4.3%; P = .67; unadjusted model: odds ratio, 1.10; 95% CI, 0.82-1.47; fully adjusted model: odds ratio, 1.12; 95% CI, 0.83-1.51). Results were stable across sensitivity analyses with a QFR threshold of 0.78 and 0.75. CONCLUSIONS: Target vessel QFR >0.80 was associated with a significantly higher risk of arterial graft occlusion at 12 months after coronary artery bypass grafting surgery. No significant association was found between target lesion QFR and vein graft occlusion.

First-in-human evaluation of a novel ultrathin sirolimus-eluting iron bioresorbable scaffold: 3-year outcomes of the IBS-FIM trial.

BACKGROUND: The first-generation polymeric bioresorbable scaffolds resulted in higher than acceptable 3-year rates of device-related adverse outcomes. AIMS: We aimed to assess the intermediate-term safety and performance of a novel ultrathin-strut sirolimus-eluting iron bioresorbable scaffold (IBS) in non-complex coronary lesions. METHODS: The prospective, single-arm, open-label IBS first-in-human study enrolled 45 patients, each with a single de novo lesion. Enrolled patients were randomly assigned to 2 follow-up cohorts. Angiographic and imaging follow-up with intravascular ultrasound and optical coherence tomography (OCT) were conducted at 6 and 24 months in cohort 1 (n=30) and at 12 and 36 months in cohort 2 (n=15). Clinical follow-up was conducted at 1, 6 and 12 months, and annually thereafter up to 5 years. The coprimary outcomes were target lesion failure (TLF) and angiographic late lumen loss (LLL) at 6 months. RESULTS: A total of 45 patients were enrolled between April 2018 and January 2019. The mean age was 53.2 years, 77.8% were male, and 26.7% had diabetes. The TLF rates were 2.2% at 6 months and 6.7% at 3 years, which in all cases were due to clinically indicated target lesion revascularisation. No deaths, myocardial infarctions or stent thromboses occurred during 3-year follow-up. In-scaffold LLL was 0.33±0.27 mm at 6 months and 0.37±0.57 mm at 3 years. By OCT, the proportion of covered struts was 99.8% at 6 months and 100% after 1 year. The 3-year strut absorption rate was 95.4%. CONCLUSIONS: In this first-in-human experience, an ultrathin IBS was safe and effective for the treatment of de novo non-complex coronary lesions up to 3-year follow-up.

Simultaneous Hybrid Coronary Revascularization vs Conventional Strategies for Multivessel Coronary Artery Disease: A 10-Year Follow-Up.

BACKGROUND: Although evidence is sufficient to confirm that hybrid coronary revascularization (HCR) is safe and effective in the short term, its value in the long run is debatable. OBJECTIVES: This study sought to compare the long-term outcomes of HCR with coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) for multivessel disease. METHODS: Three groups of patients, 540 each, receiving HCR, CABG, or PCI between June 2007 to September 2018, were matched using propensity score matching. Patients were stratified by EuroSCORE (European System for Cardiac Operative Risk Evaluation) II (low ≤0.9; 0.9 < medium <1.5; high ≥1.5) and SYNTAX (Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery) score (low ≤22; 22 < medium <33; high ≥33). Major adverse cardiac and cerebrovascular events (MACCE) and Seattle Angina Questionnaire (SAQ) scores were compared among the 3 groups. RESULTS: In terms of MACCE and SAQ, HCR performed similarly to off-pump CABG but significantly outperformed PCI (P < 0.001). In the low-to-medium EuroSCORE II and medium-to-high SYNTAX score tertiles, MACCE rates in the HCR group were significantly lower than those in the PCI (EuroSCORE II: low, 30.7% vs 41.2%; P = 0.006; medium, 31.3% vs 41.7%; P = 0.013; SYNTAX score: medium, 27.6% vs 41.2%; P = 0.018; high, 32.4% vs 52.7%; P = 0.011) but were similar to those in the CABG group. In the high EuroSCORE II stratum, HCR had a lower MACCE rate than CABG (31.9% vs 47.0%; P = 0.041) and PCI (31.9% vs 53.7%; P = 0.015). CONCLUSIONS: Compared with conventional strategies, HCR provided satisfactory long-term outcomes in MACCE and functional status for multivessel disease.

Coronary Artery Bypass Grafting and Percutaneous Coronary Intervention in Patients With Chronic Total Occlusion and Multivessel Disease.

BACKGROUND: Percutaneous coronary intervention (PCI) has been used increasingly as an alternative means of revascularization for patients with chronic total occlusion and multivessel disease. We investigated 5-year clinical outcomes following coronary artery bypass grafting (CABG) and PCI in patients with chronic total occlusion and multivessel disease. METHODS: In this single-center, retrospective cohort study, 4324 consecutive patients with ≥1 chronic total occlusion and multivessel disease were treated with either CABG (n=2264) or PCI (n=2060) between 2010 and 2013. The primary outcome was 5-year composite of death, myocardial infarction, or stroke. An inverse-probability-of-treatment weighting method was used adjusting for both patient and lesion characteristics. RESULTS: The unadjusted 5-year composite outcomes were similar between CABG group and PCI group (12.1% [258/2264] versus 11.4% [218/2060]; P=0.52). After adjustment for baseline variables, PCI was associated with significantly higher risk of composite outcomes (adjusted hazard ratio: 1.21 [95% CI, 1.02-1.44]; P=0.03). The inferiority of PCI in 5-year composite outcome was significant in patients with CABG recommendation according to SYNTAX (Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery) score II (adjusted hazard ratio: 1.55 [95% CI, 1.14-2.09]; P=0.005) but not evident in patients with PCI or PCI/CABG equipoise recommendation according to SYNTAX score II (adjusted hazard ratio: 0.94 [95% CI, 0.75-1.17]; P=0.56). A similar risk of 5-year composite outcomes was observed between CABG and PCI with residual SYNTAX score ≤8. CONCLUSIONS: In this single-center retrospective study among patients with chronic total occlusion and multivessel disease, PCI was associated with higher risk of 5-year composite death, myocardial infarction, or stroke.

Association of symptom status, myocardial viability, and clinical/anatomic risk on long-term outcomes after chronic total occlusion percutaneous coronary intervention.

OBJECTIVES: This study aimed to examine the association of less-certain indication of chronic total occlusion percutaneous coronary intervention (CTO-PCI) with subsequent clinical outcomes. BACKGROUND: The impact of patient symptoms, myocardial viability, and clinical and anatomic risk on long-term outcomes is underdetermined. METHODS: Consecutive patients undergoing CTO-PCI at a large-volume single center between 2010 and 2013 were included. Central adjudication was used to assess the appropriateness of three prespecified indications. The primary outcome was the 5-year composite endpoint of death or myocardial infarction (MI). RESULTS: Of 2,659 patients with 2,735 CTO lesions, the 348 (13.1%) asymptomatic patients, 164 (6.2%) patients without viable myocardium in the CTO territory, and 306 (11.5%) patients in whom the Synergy between PCI with Taxus and Cardiac Surgery Score II favored coronary artery bypass grafting (CABG) had higher 5-year death or MI compared with the rest patients in each category (12.0% vs. 8.6%, p = .04; 16.3% vs. 8.5%, p < .0001; 12.2% vs. 8.6%, p = .03), respectively. Multivariable regression analysis demonstrated that without symptom (hazard ratio: 1.51; 95% confidence interval: 1.06-2.15; p = .02), non-viable myocardium in CTO territory (hazard ratio: 1.77; 95% confidence interval: 1.16-2.72; p = .009), and deemed more favorable for CABG (hazard ratio:1.54; 95% confidence interval: 1.04-2.28; p = .03), but not the technical success (hazard ratio:0.85; 95% confidence interval: 0.62-1.18; p = .34), were independent predictors for the primary endpoint. CONCLUSIONS: In this large cohort of CTO-PCI, those who were asymptomatic, non-viable myocardium in the CTO territory, or deemed more favorable for CABG were associated with higher risk of long-term mortality or MI.

Prognostic Value of Quantitative Flow Ratio Based Functional SYNTAX Score in Patients With Left Main or Multivessel Coronary Artery Disease.

BACKGROUND: The potential impact of quantitative flow ratio (QFR) based functional Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery (SYNTAX) score (FSSQFR) on prognostication and revascularization strategy choice has not been fully investigated, and the discriminant ability of FSSQFR needs further validation. METHODS: QFR was retrospectively analyzed in left main or patients with multivessel coronary artery disease from the PANDA III trial. A total of 607 patients with analyzable QFR in all vessels were included. FSSQFR was counted by summing the individual scores only in ischemia-producing lesions (vessel QFR ≤0.8). Patients were stratified according to tertiles of SYNTAX score (SS), and 3 groups of FSS were divided by the same cutoff score. The primary end point was 2-year major adverse cardiac events (a composite of cardiac death, any myocardial infarction, or ischemia-driven revascularization). RESULTS: After calculating the FSSQFR, 16% (96/607) of study patients moved from higher-risk group by SS to lower-risk group. In the low, intermediate, and high FSSQFR group, the cumulative incidence of 2-year major adverse cardiac events was 9.1%, 13.5%, and 22.3% (P=0.0004), and the rate of a composite of cardiac death or myocardial infarction (3.8%, 7.3%, and 13.7%, P=0.0006) was also increased. Compared with SS, FSSQFR significantly improved risk classification and prognostication (area under the curve of the receiver-operating characteristics 0.65 versus 0.62, P=0.0009). Moreover, 6% (38/607) of patients, for whom coronary artery bypass grafting would be recommended according to SS, converted to favor percutaneous coronary intervention after FSSQFR calculation. After multivariate adjustment, FSSQFR was an independent predictor of 2-year major adverse cardiac events (adjusted hazard ratio, 1.05 [95% CI, 1.02-1.07]; P=0.0001). CONCLUSIONS: Among patients with left main or multivessel coronary artery disease, FSSQFR showed applicability in prognostication and revascularization strategy choice. An improved scoring system combining anatomy and physiology (FSSQFR) discriminated the risk of adverse events modestly better than anatomic assessment (SS) alone. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02017275. Graphic Abstract: A graphic abstract is available for this article.

Mis-estimation of coronary lesions and rectification by SYNTAX score feedback for coronary revascularization appropriateness.

BACKGROUND: Imprecise interpretation of coronary angiograms was reported and resulted in inappropriate revascularization. Synergy Between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery (SYNTAX) score is a comprehensive system to evaluate the complexity of the overall lesions. We hypothesized that a real-time SYNTAX score feedback from image analysts may rectify the mis-estimation and improve revascularization appropriateness in patients with stable coronary artery disease (CAD). METHODS: In this single-center, historical control study, patients with stable CAD with coronary lesion stenosis ≥50% were consecutively recruited. During the control period, SYNTAX scores were calculated by treating cardiologists. During the intervention period, SYNTAX scores were calculated by image analysts immediately after coronary angiography and were provided to cardiologists in real-time to aid decision-making. The primary outcome was revascularization deemed inappropriate by Chinese appropriate use criteria for coronary revascularization. RESULTS: A total of 3245 patients were enrolled and assigned to the control group (08/2016-03/2017, n = 1525) or the intervention group (03/2017-09/2017, n = 1720). For SYNTAX score tertiles, 17.9% patients were overestimated and 4.3% were underestimated by cardiologists in the control group. After adjustment, inappropriate revascularization significantly decreased in the intervention group compared with the control group (adjusted odds ratio [OR]: 0.83; 95% confidence interval [CI]: 0.73-0.95; P = 0.007). Both inappropriate percutaneous coronary intervention (adjusted OR: 0.82; 95% CI: 0.74-0.92; P < 0.001) and percutaneous coronary intervention utilization (adjusted OR: 0.88; 95% CI: 0.79-0.98; P = 0.016) decreased significantly in the intervention group. There was no significant difference in 1-year adverse cardiac events between the control group and the intervention group. CONCLUSIONS: Real-time SYNTAX score feedback significantly reduced inappropriate coronary revascularization in stable patients with CAD. CLINICAL TRIAL REGISTRATION: Nos. NCT03068858 and NCT02880605; https://www.clinicaltrials.gov.

Validation of the long-term prognostic capability of the SYNTAX score II in patients undergoing biodegradable polymer-based Sirolimus-eluting stents: 2-year outcomes from the PANDA III trial.

BACKGROUND: This study aimed to assess the prognostic ability of SYNTAX (Synergy Between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery) Score II (SS-II) in LM and/or TVD patients undergoing biodegradable polymer-based drug-eluting stents (BP-DES) in the multi-central randomized PANDA III trial. METHODS: A total of 723 patients in PANDA III population were enrolled in this study. According to SS-II tertiles, patients were stratified as follow: SS-II ≤ 23 (n = 224), 23 < SS II ≤ 31 (n = 255), SS II > 31 (n = 244). The predictive abilities for 2-year cardiac death were compared between angiographic scores and scores combining both angiographic and clinical variables. RESULTS: Mean anatomic SS was 20.6 ± 9.4, SS-II for PCI was 28.7 ± 8.6. During 2-year follow up, cardiac death (0.00% vs. 1.7% vs. 4.3%, p = 0.003) and target lesion failure (5.9% vs. 9.1% vs. 13.6%, p = 0.020) was significantly higher in the upper tertile group than in intermedian and low tertile. At multivariate analysis, SS-II for PCI was an independent risk factor of cardiac death (Hazard ratio: 2.41, 95%CI: 1.47-3.97, p < 0.005) and TLF (Hazard ratio: 1.29, 95%CI: 1.01-1.65, p = 0.040). The ROC curve analysis showed that SS-II for PCI had better ability than other SYNTAX scoring systems to predict cardiac death (AUC: 0.746, 95%CI:0.63-0.87, p = 0.010). CONCLUSIONS: The SS-II had superiority than other SYNTAX scoring systems in predicting 2-year cardiac death in LM and/or TVD patients undergoing PCI with biodegradable polymer drug-eluting stents.

Quantitative flow ratio-guided strategy versus angiography-guided strategy for percutaneous coronary intervention: Rationale and design of the FAVOR III China trial.

BACKGROUND: Quantitative flow ratio (QFR) is a novel angiography-based approach enabling fast computation of fractional flow reserve without use of pressure wire or adenosine. The objective of this investigator-initiated, multicenter, patient- and clinical assessor-blinded randomized trial is to evaluate the efficacy and cost-effectiveness of a QFR-augmented angiography-guided (QFR-guided) strategy versus an angiography-only guided (angiography-guided) strategy for percutaneous coronary intervention (PCI) in patients with coronary artery disease. METHODS: Approximately 3,830 patients will be randomized in a 1:1 ratio to a QFR-guided or an angiography-guided strategy. Included subjects scheduled for coronary angiography have at least 1 lesion eligible for PCI with 50%-90% stenosis in an artery with ≥2.5 mm reference diameter. Subjects assigned to the QFR-guided strategy will have QFR measured in each interrogated vessel and undergo PCI when QFR ≤0.80, with deferral for lesions with QFR >0.80. Those assigned to the angiography-guided strategy will undergo PCI based on angiography. Optimal medical therapy will be administered to all treated and deferred patients. The primary end point is the 1-year rate of major adverse cardiac events (MACE), a composite of all-cause mortality, any myocardial infarction, or any ischemia-driven revascularization. The major secondary end point is 1-year MACE excluding periprocedural myocardial infarction. Other secondary end points include the individual components of MACE and cost-effectiveness end points. The sample size affords 85% power to demonstrate superiority of QFR guidance compared with angiography guidance. CONCLUSIONS: The FAVOR III China study will be the first randomized trial to examine the effectiveness and cost-effectiveness of a QFR-guided versus an angiography-guided PCI strategy in coronary artery disease patients.

A modified predilation, sizing, and postdilation scoring system for patients undergoing metallic drug-eluting stent implantations.

OBJECTIVE: This study sought to assess whether the predilation, scaffold/stent sizing, and postdilation (PSP) score for bioresorbable scaffold (BRS) implantation was associated with outcomes following metallic drug-eluting stent (DES) implantation. BACKGROUND: The PSP score is associated with patients' prognoses after BRS implantation. METHODS: This study involved 2,348 patients who underwent biodegradable polymer DES implantations during the PANDA III trial. The optimal PSP technique was defined according to previous studies of BRS implantations. The main outcome was target lesion failure (TLF) that comprised cardiac death, target-vessel myocardial infarction, or ischemia-driven target lesion revascularization. RESULTS: Twenty-five (1.1%) patients fulfilled all the PSP criteria. The BRS-derived PSP score was of limited prognostic value for 2-year TLF after metallic DES implantation; optimal sizing was a protective factor, but optimal predilation was a risk factor. We built a new PSP model for DESs by identifying the following risk factors: predilation performed with a residual stenosis ≥70% or a balloon-to-quantitative coronary angiography (QCA)-determined reference vessel diameter (RVD) ratio >1:1, sizing performed with an RVD <2.25 mm or a stent diameter >0.25 mm wider than the QCA-RVD, a postprocedural stenosis diameter ≥30%, age, and the baseline SYNergy between percutaneous coronary intervention with TAXus and cardiac surgery (SYNTAX) score. The new PSP scoring system predicted 2-year TLF (area under the curve, 0.69; 95% confidence interval, 0.65-0.73); a cutoff value of 19.2 points identified high-risk patients. CONCLUSIONS: The new PSP scoring system, based on redefined PSP criteria, age, and the SYNTAX score, could help optimize metallic DES implantations.

Intravascular Ultrasound Guidance Improves the Long-term Prognosis in Patients with Unprotected Left Main Coronary Artery Disease Undergoing Percutaneous Coronary Intervention.

This study compared the long term outcomes in patients with unprotected left main coronary artery (LMCA) disease who underwent stenting under the guidance of intravascular ultrasound (IVUS) or conventional angiography at a large single center. The primary outcome was the composite of all-cause death and myocardial infarction (MI) at 3 years. Target vessel revascularization (TVR) at 3 years was one of the secondary outcomes. Between January 2004 and December 2011, a total of 1,899 patients who underwent IVUS-guided (n = 713, 37.5%) or conventional angiography-guided (n = 1186, 62.5%) stenting were included. At 3 years, the unadjusted primary outcome trended lower in the IVUS-guided group versus the angiography-guided (6.9% vs. 8.4%, p = 0.22) although the TVR was similar between two groups (6.0% vs. 6.0%, p = 0.97). However, after adjustment for differences in baseline risk factors, IVUS-guidance was associated with significantly lower incidence of the composite of all-cause death and MI (hazard ratio [HR]: 0.65; 95% confidence interval [CI]: 0.50 to 0.84; p = 0.001), although there was still no significant difference in TVR between the two groups (HR: 1.09; 95% CI: 0.84 to 1.42; p = 0.53). IVUS guidance has benefits in improving the long-term prognosis for unprotected LMCA stenting.

Impact of Operator Experience and Volume on Outcomes After Left Main Coronary Artery Percutaneous Coronary Intervention.

OBJECTIVES: The aim of this study was to assess the impact of operator experience on prognosis after left main coronary artery (LM) percutaneous coronary intervention (PCI). BACKGROUND: LM PCI can be technically challenging and potentially risky considering the amount of supplied myocardium. METHODS: Consecutive patients who underwent unprotected LM PCI at a single institution were included and compared according to whether the primary operator was an experienced, high-volume LM operator (defined as an operator who performed at least 15 LM PCIs per year for at least 3 consecutive years) or not. Kaplan-Meier estimates and Cox proportional hazards models are presented. RESULTS: From January 2004 to December 2011, a total of 1,948 patients underwent unprotected LM PCI by 25 operators. Of these, 7 operators (28%) were considered experienced, and 18 (72%) were considered less experienced, with an overall mean experience of 12.0 ± 11.5 LM PCIs per year. LM PCI was performed in 1,422 patients (73%) by experienced operators and in 526 patients (27%) by less experienced operators. Patients treated by experienced operators had more complex and extensive coronary artery disease. Unadjusted and adjusted risks for cardiac death were lower for patients who were treated by experienced operators, both at 30-day (unadjusted hazard ratio [HR]: 0.23; 95% confidence interval [CI]: 0.09 to 0.60; p = 0.003; adjusted HR: 0.22; 95% CI: 0.09 to 0.59; p = 0.003) and 3-year (unadjusted HR: 0.53; 95% CI: 0.32 to 0.89, p = 0.02; adjusted HR: 0.49; 95% CI: 0.29 to 0.84; p = 0.009) follow-up. Discrimination improved when operator experience was added to Cox proportional hazards models containing the SYNTAX (Synergy Between PCI With Taxus and Cardiac Surgery) score (integrated discriminatory index = 0.004, p = 0.03) or SYNTAX score II (integrated discriminatory index = 0.007, p = 0.02). No significant interaction was detected between operator experience and distal bifurcation LM lesion, 2-stent bifurcation stenting, and intravascular ultrasound use (p > 0.10 for all). CONCLUSIONS: Patients who underwent LM PCI by high-volume and experienced operators had better short- and long-term prognoses. Operator experience is an important factor in a complex intervention such as LM PCI.

Coronary Artery Bypass Graft Surgery and Percutaneous Coronary Interventions in Patients With Unprotected Left Main Coronary Artery Disease.

OBJECTIVES: This study sought to investigate long-term clinical outcomes following coronary artery bypass graft (CABG) and percutaneous coronary intervention (PCI) in patients with unprotected left main disease (ULMD). BACKGROUND: PCI has been increasingly used as an alternative mode of revascularization for ULMD. However, there are limited data comparing clinical outcomes between CABG surgery and PCI. METHODS: Between 2004 and 2010, 4,046 consecutive patients with ULMD were treated with either CABG surgery (n = 2,604) or PCI (n = 1,442) with drug-eluting stents. The primary outcome was 3-year all-cause mortality and the secondary outcome was the composite of death, nonfatal myocardial infarction, or nonfatal stroke. RESULTS: The unadjusted 3-year all-cause mortality was higher in the PCI group as compared with the CABG group (3.8% vs. 2.5%; log-rank p = 0.03), although there was no significant difference in the composite outcome (7.5% vs. 9.4%; log-rank p = 0.07). After adjustment for differences in baseline risk factors, PCI was associated with significantly higher risk of all-cause mortality (hazard ratio [HR]: 1.71; 95% confidence interval [CI]: 1.32 to 2.21; p < 0.001) but similar risk of the composite outcome (HR: 0.94; 95% CI: 0.82 to 1.09; p = 0.43). These differences were not statistically significant among patients with low or intermediate SYNTAX (Synergy Between PCI With Taxus and Cardiac Surgery) score (≤32) or diabetes; however, PCI was associated with an increased risk among those with high SYNTAX score (>32), with HRs of 3.10 (95% CI: 1.84 to 5.22; p < 0.001) for all-cause mortality and 1.82 (95% CI: 1.36 to 2.45; p < 0.001) for the composite outcome. CABG was associated with lower risk of repeat revascularization but higher risk of stroke in each clinically relevant subgroup. CONCLUSIONS: In this single-center observational study among patients with ULMD, CABG was associated with improved long-term outcomes, especially in patients with more complex disease.

Six Versus 12 Months of Dual Antiplatelet Therapy After Implantation of Biodegradable Polymer Sirolimus-Eluting Stent: Randomized Substudy of the I-LOVE-IT 2 Trial.

BACKGROUND: There are no reports on a large-scale randomized trial exploring optimal dual antiplatelet therapy (DAPT) duration after biodegradable polymer sirolimus-eluting stent implantation. We sought to report the outcomes of a randomized substudy of the prospective Evaluate Safety and Effectiveness of the Tivoli DES and the Firebird DES for Treatment of Coronary Revascularization (I-LOVE-IT 2) trial. METHODS AND RESULTS: In the prospective noninferiority randomized I-LOVE-IT 2 trial, 1829 patients allocated to the biodegradable polymer sirolimus-eluting stent group were also randomized to receive either 6-month (n=909) or 12-month DAPT (n=920). The primary end points of this noninferiority substudy were 12-month target lesion failure (composite of cardiac death, target vessel myocardial infarction or clinically indicated target lesion revascularization), and the major secondary end points were 12-month net adverse clinical and cerebral events (composite of all-cause death, all myocardial infarction, stroke, or major bleeding [Bleeding Academic Research Consortium type ≥3]). The 12-month target lesion failure in 6-month DAPT group was comparable with the 12-month DAPT group (6.8% versus 5.9%; difference and 95% confidence interval, 0.87% [-1.37% to 3.11%], P for noninferiority=0.0065). Further follow-up at 18 months showed that incidence of target lesion failure and net adverse clinical and cerebral events were similar between the 2 groups (7.5% versus 6.3%, log-rank P=0.32; 7.8% versus 7.3%, log-rank P=0.60; respectively), as well as their individual end point components. CONCLUSIONS: This study indicated noninferiority in safety and efficacy of 6-month versus 12-month DAPT after implantation of a novel biodegradable polymer sirolimus-eluting stent. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01681381.

Delivery of demineralized bone matrix powder using a salt-leached silk fibroin carrier for bone regeneration.

Demineralized bone matrix (DBM) has been widely used for bone regeneration due to its osteoinductivity and osteoconductivity. However, the use of DBM powder is limited due to the difficulties in handling, the tendency to migrate from graft sites and the lack of stability after surgery. In this study, a mechanically stable, salt-leached porous silk fibroin carrier was used to improve the handling properties of DBM powder and to support the attachment, proliferation and osteogenic differentiation of rat bone marrow derived mesenchymal stem cells (rBMSCs). The DBM-silk fibroin (DBM/SF) scaffolds were fabricated with different contents of DBM powder (0%, 10%, 20%, 40% and 80% DBM/SF scaffolds). It was found that the DBM/SF scaffolds could form a stable composite preventing the migration of DBM powder. Moreover, the microarchitecture and mechanical properties of the scaffolds were influenced by the DBM powder. rBMSCs were seeded on the DBM/SF scaffolds and cultured for 14 days. Cell proliferation assays and cell morphology observations indicated that 20% DBM/SF scaffolds exhibited good cell attachment and proliferation. In addition, compared with the other groups, the cellular function was more actively exhibited on 20% DBM/SF scaffolds, as evident by the real-time reverse transcriptase-polymerase chain reaction (RT-PCR) analysis for osteoblast-related gene markers (e.g. COL1A1, ALP and cbfa1), the immunocytochemical evaluations of osteoblast-related extracellular matrix components (e.g. COL1A1, OCN and ONN) and the ALP activities. All the data suggested that DBM powder could be delivered using a silk fibroin carrier with improved handling characteristics and that 20% DBM/SF scaffolds had great potential as osteogenesis promoting scaffolds for successful applications in bone regeneration.