Development and validation of a model integrating clinical and coronary lesion-based functional assessment for long-term risk prediction in PCI patients.

OBJECTIVES: To establish a scoring system combining the ACEF score and the quantitative blood flow ratio (QFR) to improve the long-term risk prediction of patients undergoing percutaneous coronary intervention (PCI). METHODS: In this population-based cohort study, a total of 46 features, including patient clinical and coronary lesion characteristics, were assessed for analysis through machine learning models. The ACEF-QFR scoring system was developed using 1263 consecutive cases of CAD patients after PCI in PANDA III trial database. The newly developed score was then validated on the other remaining 542 patients in the cohort. RESULTS: In both the Random Forest Model and the DeepSurv Model, age, renal function (creatinine), cardiac function (LVEF) and post-PCI coronary physiological index (QFR) were identified and confirmed to be significant predictive factors for 2-year adverse cardiac events. The ACEF-QFR score was constructed based on the developmental dataset and computed as age (years)/EF (%) + 1 (if creatinine ≥ 2.0 mg/dL) + 1 (if post-PCI QFR ≤ 0.92). The performance of the ACEF-QFR scoring system was preliminarily evaluated in the developmental dataset, and then further explored in the validation dataset. The ACEF-QFR score showed superior discrimination (C-statistic = 0.651; 95% CI: 0.611-0.691, P < 0.05 versus post-PCI physiological index and other commonly used risk scores) and excellent calibration (Hosmer-Lemeshow χ2 = 7.070; P = 0.529) for predicting 2-year patient-oriented composite endpoint (POCE). The good prognostic value of the ACEF-QFR score was further validated by multivariable Cox regression and Kaplan-Meier analysis (adjusted HR = 1.89; 95% CI: 1.18-3.04; log-rank P < 0.01) after stratified the patients into high-risk group and low-risk group. CONCLUSIONS: An improved scoring system combining clinical and coronary lesion-based functional variables (ACEF-QFR) was developed, and its ability for prognostic prediction in patients with PCI was further validated to be significantly better than the post-PCI physiological index and other commonly used risk scores.

Impact of Relative Improvement in Quantitative Flow Ratio on Clinical Outcomes After Percutaneous Coronary Intervention　- A Subanalysis of the PANDA III Trial.

BACKGROUND: The clinical impact of relative improvements in coronary physiology in patients receiving percutaneous coronary intervention (PCI) for coronary artery disease (CAD) remains undetermined. METHODS AND RESULTS: The quantitative flow ratio (QFR) recovery ratio (QRR) was calculated in 1,424 vessels in the PANDA III trial as (post-PCI QFR-pre-PCI QFR)/(1-pre-PCI QFR). The primary endpoint was the 2-year vessel-oriented composite endpoint (VOCE; a composite of vessel-related cardiac death, vessel-related non-procedural myocardial infarction, and ischemia-driven target vessel revascularization). Study vessels were dichotomously stratified according to the optimal QRR cut-off value. During the 2-year follow-up, 41 (2.9%) VOCEs occurred. Low (<0.86) QRR was associated with significantly higher rates of 2-year VOCEs than high (≥0.86) QRR (6.6% vs. 1.4%; adjusted hazard ratio [aHR] 5.05; 95% confidence interval [CI] 2.53-10.08; P<0.001). Notably, among vessels with satisfactory post-procedural physiological results (post-PCI QFR >0.89), low QRR also conferred an increased risk of 2-year VOCEs (3.7% vs. 1.4%; aHR 3.01; 95% CI 1.30-6.94; P=0.010). Significantly better discriminant and reclassification performance was observed after integrating risk stratification by QRR and post-PCI QFR to clinical risk factors (area under the curve 0.80 vs. 0.71 [P=0.010]; integrated discrimination improvement 0.05 [P<0.001]; net reclassification index 0.64 [P<0.001]). CONCLUSIONS: Relative improvement of coronary physiology assessed by QRR showed applicability in prognostication. Categorical classification of coronary physiology could provide information for risk stratification of CAD patients.

Left main bifurcation stenting: impact of residual ischaemia on cardiovascular mortality.

AIMS: The present study sought to determine the rate and prognostic implications of post-procedural physiologically significant residual ischemia according to Murray law-based quantitative flow ratio (µQFR) after left main (LM) bifurcation percutaneous coronary intervention (PCI). METHODS AND RESULTS: Consecutive patients undergoing LM bifurcation stenting at a large tertiary care center between January 2014 and December 2016 with available post-PCI µQFR were included. Physiologically significant residual ischemia was defined by post-PCI µQFR values ≤0.80 in the left anterior descending (LAD) or left circumflex artery (LCX). The primary outcome was 3-year cardiovascular death. The major secondary outcome was 3-year bifurcation-oriented composite endpoint (BOCE). Among 1170 included patients with analyzable post-PCI µQFR, 155 (13.2%) had residual ischemia in either LAD or LCX. Patients with vs. those without residual ischemia had a higher risk of 3-year cardiovascular mortality [5.4% vs. 1.3%; adjusted hazard ratio (HR) 3.20, 95% confidence interval (CI): 1.16-8.80]. The 3-year risk of BOCE was significantly higher in the residual ischemia group (17.8% vs. 5.8%; adjusted HR 2.79, 95% CI: 1.68-4.64), driven by higher incidence of the composite of cardiovascular death and target bifurcation-related myocardial infarction (14.0% vs. 3.3%; adjusted HR 4.06, 95% CI: 2.22-7.42). A significant, inverse association was observed between continuous post-PCI µQFR and the risk of clinical outcomes (per 0.1 µQFR decrease, HR of cardiovascular death 1.27, 95% CI: 1.00-1.62; HR of BOCE 1.29, 95% CI: 1.14-1.47). CONCLUSION: After angiographically successful LM bifurcation PCI, residual ischemia assessed by µQFR was identified in 13.2% of patients and was associated with higher risk of 3-year cardiovascular death, indicating the superior prognostic value of post-PCI physiological assessment.

Prognostic Implications of Quantitative Flow Ratio-Derived Physiological 2-Dimensional Residual Disease Patterns After Stenting.

BACKGROUND: Post-percutaneous coronary intervention (PCI) residual disease is associated with clinical outcomes. Nevertheless, the prognostic value of residual disease patterns remains unknown. OBJECTIVES: This study aimed to evaluate clinical implications of 2-dimensional residual disease patterns after PCI. METHODS: One thousand six hundred seven vessels that underwent successful PCI were included. Two-dimensional residual disease patterns were determined by visual assessment or the quantitative flow ratio (QFR)-derived pull back pressure gradient index (with a cutoff value of 0.78 to define predominant focal versus diffuse disease) and instantaneous QFR gradient per unit length (with a cutoff value of ≥0.005/mm to define a major gradient). The clinical outcome was the 2-year vessel-oriented composite outcome (VOCO). RESULTS: Residual disease patterns were classified into 4 groups: predominant focal without and with a major gradient (group 1 [n = 1,058] and group 2 [n = 63], respectively) and predominant diffuse without and with a major gradient (group 3 [n = 318] and group 4 [n = 168], respectively). At 2 years, VOCO was lowest in group 1 (1.4% vs 5.4% in group 2 vs 4.8% in group 3 vs 8.5% in group 4, all P < 0.05), whereas there was no prognostic value for classifications by visual assessment. Physiological residual disease patterns were independently associated with VOCO and showed increased prognostic value when introduced to a model with clinical risk factors only (C index: 0.77 vs. 0.68, P = 0.008; net reclassification improvement: 0.65, P < 0.001; integrated discrimination improvement: 0.020, P < 0.001). CONCLUSIONS: Objective analysis of post-PCI QFR pull backs using the concept of 2-dimensional residual disease patterns is feasible and superior to visual assessments. The residual disease patterns were independently associated with VOCO at 2 years.

Prognostic Implications of Prestent Pullback Pressure Gradient and Poststent Quantitative Flow Ratio in Patients Undergoing Percutaneous Coronary Intervention.

Background Coronary diffuse disease associates with poor outcomes, but little is known about its role after percutaneous coronary intervention (PCI). We aimed to investigate the prognostic implication of pre-PCI focal or diffuse disease patterns combined with post-PCI quantitative flow ratio (QFR). Methods and Results Pre-PCI QFR derived pullback pressure gradient (PPG) (QFR-PPG) was measured to assess physiological disease patterns for 1685 included vessels; the vessels were classified according to dichotomous pre-PCI QFR-PPG and post-PCI QFR. Vessel-oriented composite outcome, a composite of vessel-related ischemia-driven revascularization, vessel-related myocardial infarction, or cardiac death at 2 years was compared among these groups. Vessels with low pre-PCI PPG (3.9% versus 2.0%, hazard ratio [HR], 1.93; 95% CI, 1.08-3.44; P=0.02) or low post-PCI QFR (9.8% versus 2.7%, HR, 3.78; 95% CI, 1.61-8.87; P=0.001) demonstrated higher vessel-oriented composite outcome risk after stent implantation. Of note, despite high post-PCI QFR achieved, vessels with low pre-PCI QFR-PPG presented higher risk of vessel-oriented composite outcome than those with high pre-PCI QFR-PPG (3.7% versus 1.8%, HR, 2.03; 95% CI, 1.09-3.76; P=0.03) and pre-PCI QFR-PPG demonstrated direct prognostic effect not mediated by post-PCI QFR. Integration of groups classified by pre-PCI QFR-PPG and post-PCI QFR showed significantly higher discriminant and reclassification abilities than clinical factors (C-index 0.77 versus 0.72, P=0.03; integrated discrimination improvement 0.93%, P=0.04; net reclassification index 0.33, P=0.02). Conclusions Prognostic value of pre-PCI focal or diffuse disease patterns assessed by QFR-PPG index was retained even after successful PCI, which is mostly explained by its direct effect that was not mediated by post-PCI QFR. Integration of both pre-PCI and post-PCI physiological information can provide better risk stratification in vessels with stent implantation. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT05104580.

Effects of diabetes mellitus on post-intervention coronary physiological assessment derived by quantitative flow ratio in patients with coronary artery disease underwent percutaneous coronary intervention.

AIMS: To compare the prognostic implication of post-percutaneous coronary intervention (PCI) quantitative flow ratio (QFR) assessment in patients with and without diabetes enrolled in the all-comers, multicenter, randomized controlled PANDA III trial. METHODS: All treated vessels in PANDA III trial were retrospectively assessed for post-PCI QFR. Vessels with available post-PCI QFR were further stratified into DM and non-DM cohorts, and prognostic performance of post-PCI QFR was compared in 2 cohorts. The primary outcome was 2-year vessel-oriented composite endpoint (VOCE), defined as composite of vessel-related cardiac death, vessel-related non-procedural myocardial infarction, and ischemia-driven target vessel revascularization. RESULTS: Of 2,989 treated vessels, 2,227 (74.5%) with available post-PCI QFR were included, while 548 were presence of DM and 1,679 were not. The performance of post-PCI QFR to predict 2-year VOCE were moderate in both DM (area under the curve [AUC] 0.77, 95% confidence interval [CI]: 0.68 to 0.87) and non-DM cohorts (AUC 0.74, 95% CI: 0.67 to 0.82), while between-cohorts AUC difference was not significant (ΔAUC 0.03, P = 0.65). After multivariate adjustment, vessels with suboptimal post-PCI QFR results (≤0.92) were associated with higher risk of 2-year VOCE in both DM (adjusted HR 6.24, 95% CI: 2.40 to 16.2) and non-DM cohorts (adjusted HR 5.92, 95% CI: 3.28 to 10.7) without significant interaction (P for interaction 0.91). CONCLUSIONS: This study, the first to directly compare clinical value of post-PCI QFR assessments in patients with and without DM, showed that a higher post-PCI QFR value was associated with improved long-term prognosis regardless of the presence of DM. Clinical Trial Registration Information URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02017275.

Protective ballooning technique for prevention of side branch occlusion in coronary nonleft main true bifurcation lesions: A single-center study.

OBJECTIVES: We aimed to evaluate the efficacy of a protective ballooning technique in preventing side branch (SB) occlusion and to assess the long-term clinical outcomes for coronary nonleft main true bifurcation lesions. BACKGROUND: SB occlusion is a major complication associated with percutaneous coronary intervention (PCI) for coronary bifurcation lesions. METHODS: Patients were consecutively enrolled and randomly assigned to protective ballooning technique or jailed wire technique group. Periprocedural and long-term clinical outcomes were compared. RESULTS: Patients in the protective ballooning technique (n = 173) and jailed wire technique (n = 167) groups were followed up for 12 months. SB occlusion occurred in one patient (0.6%) and nine patients (5.4%) in each group, respectively. The proportion of thrombolysis in myocardial infarction (TIMI) flow grade 3 of the SB was higher in the protective ballooning technique group (98.8% vs. 95.2%, p < 0.05). SB rewiring was necessary in one patient in the protective ballooning technique group (0.6%) with provisional stenting, significantly lower than that in the jailed wire technique group (seven patients, 4.2%; p = 0.03). Periprocedural myocardial infarction occurred in three (1.73%) and six (3.59%) patients in the protective ballooning technique and jailed wire technique groups without significant difference, respectively. Major adverse cardiovascular events at 12 months were similar in both groups. CONCLUSIONS: Protective ballooning technique is effective for the prevention of SB occlusion in nonleft main true bifurcation lesions and had favorable long-term outcomes at the 12-month follow-up.

Post-PCI outcomes predicted by pre-intervention simulation of residual quantitative flow ratio using augmented reality.

BACKGROUND: The simulated residual quantitative flow ratio (QFR) computed from pre-intervention three-dimensional (3-D) coronary angiograms, which could theoretically predict actual post-percutaneous coronary intervention (PCI) QFR value, can be used for enhanced PCI via augmented reality. The study sought to investigate the concordance between simulated residual QFR and actual post-PCI QFR, and the prognostic value of simulated residual QFR. METHODS: QFR assessment was retrospectively performed in treated vessels from the all-comers PANDA III trial. Three-step analysis was performed: 1) concordance between simulated residual QFR and post-PCI QFR; 2) prognostic value of simulated residual QFR; and 3) forecast of outcomes by virtual randomized controlled trials (RCTs) between residual QFR and angiographic guidance. RESULTS: Of 2989 treated vessels, 2146 (71.8%) with paired analyzable simulated residual QFR and post-PCI QFR were included. The simulated residual QFR and post-PCI QFR were strongly correlated (r = 0.976). Low simulated residual QFR (≤0.92) was independently associated with higher risk of 2-year vessel-oriented composite endpoint (adjusted hazard ratio: 5.50; 95% confidence interval: 3.03 to 10.0). Based upon 5000 iterations of virtual RCTs, simulated residual QFR-guided strategy was anticipated to have a 2.6% absolute reduction of 2-year incidence of target vessel failure compared with the angiography-guided strategy. CONCLUSIONS: With high consistency to actual post-PCI QFR, the simulated residual QFR computed from pre-PCI 3-D coronary angiograms and augmented reality could predict functional outcome of the procedure and 2-year prognosis. Using data from PANDA III trial, the present study forecasted superiority of residual QFR-guided PCI strategy over angiographic guidance. Clinical Trial Registration Information URL: https://www.clinicaltrials.gov; Unique identifier: NCT02017275.

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.

Automatic construction of coronary artery tree structure based on vessel blood flow tracking.

We sought to propose an innovative vessel blood flow tracking (VBFT) method to extract coronary artery tree (CAT) and to assess the effectiveness of this VBFT versus the single-frame method. Construction of a CAT from a segmented artery is the basis of artificial intelligence-aided angiographic diagnosis. However, construction of a CAT using a single frame remains challenging, due to bifurcations and overlaps in two-dimensional angiograms. Overall, 13,222 angiograms, including 28,539 vessels, were retrospectively collected from 3275 patients and were then annotated. Coronary arteries were automatically segmented by a previously established deep neural networks (DNNs), and the skeleton lines were then extracted from segmentation images to construct CAT using the single-frame method and the VBFT method. Additionally, 1322 angiograms with 2201 vessels were used to test these two methods. Compared to the single-frame method, the VBFT method can significantly improve the accuracy of CAT as (84.3% vs. 72.3%; p < 0.001). Overlap (OV) was higher in the VBFT group than that in the Single-Frame group (91.1% vs. 87.5%; p < 0.001). The VBFT method significantly reduced the incidence of the lack of branching (7.30% vs. 13.9%, p < 0.001), insufficient length (6.70% vs. 11.0%, p < 0.001), and redundant branches (1.60% vs. 3.10%, p < 0.001). The VBFT method improved the extraction of a CAT structure, which will facilitate the development of artificial intelligence-aided angiographic diagnosis. Cardiologists can efficiently diagnose CAD using this method.

Outcomes of quantitative flow ratio-based percutaneous coronary intervention in an all-comers study.

BACKGROUND: Quantitative flow ratio (QFR) is a novel angiography-based physiological index for fast computation of fractional flow reserve without the use of a pressure wire or induction of hyperaemia. AIMS: We sought to investigate the prevalence and prognostic implications of achieving physiology-consistent percutaneous coronary intervention (PCI) according to the baseline angiographic QFR in an all-comers cohort. METHODS: QFR was retrospectively analysed from the angiograms of 1,391 patients enrolled in the randomised PANDA III trial. Patients in whom all functionally ischaemic vessels (baseline QFR ≤0.80) were treated and in whom all non-ischaemic vessels (baseline QFR >0.80) were deferred were termed as having had QFR-consistent treatment; otherwise, they were termed as having had QFR-inconsistent treatment. The major outcome was two-year major adverse cardiac events (MACE; a composite of all-cause death, all myocardial infarction (MI), or any ischaemia-driven revascularisation). RESULTS: Overall, 814 (58.5%) patients had QFR-consistent PCI, while 577 (41.5%) patients received QFR-inconsistent PCI. Patients with QFR-consistent versus those with QFR-inconsistent treatment had a lower risk of two-year MACE (8.4% vs 14.7%; hazard ratio [HR] 0.56, 95% confidence interval [CI]: 0.41-0.78). After adjusting for differences in baseline covariates, two-year rates of MACE remained significantly lower in the QFR-consistent group (8.8% vs 13.6%; adjusted HR 0.64, 95% CI: 0.44-0.93), due mainly to reduced ischaemia-driven revascularisation (2.9% vs 8.0%; adjusted HR 0.35, 95% CI: 0.20-0.60). CONCLUSIONS: In this post hoc analysis of an all-comers PCI trial, approximately 60% of patients were treated in accordance with what the QFR measurement would have recommended, the achievement of which was associated with improved two-year clinical outcomes. ClinicalTrials.gov identifier: NCT02017275.

Integrated coronary disease burden and patterns to discriminate vessels benefiting from percutaneous coronary intervention.

OBJECTIVE: To evaluate the prognostic implications of atherosclerosis functional pattern on ischemia-causing vessels received percutaneous coronary intervention (PCI) or conservative treatment. BACKGROUND: Quantitative flow ratio (QFR)-derived pullback pressure gradient (PPG) index is recently proposed to characterize atherosclerosis functional pattern, but its prognostic value remains unclear. METHODS: QFR-derived PPG index was retrospectively calculated in patients from the PANDA III trial. Vessels with low or high PPG treated by PCI or not were compared for the risk of 2-year vessel-oriented composite outcome (VOCO), which was a composite of vessel-related ischemia-driven revascularization, vessel-related myocardial infarction, or cardiac death. RESULTS: A total of 1444 vessels were included while 94 (6.5%) VOCOs occurred within 2 years. Among physiologically ischemic vessels (QFR ≤ 0.80) treated by PCI, those with low PPG acquired higher VOCO risk than those with high PPG (8.4% vs. 3.8%; adjusted hazard ratio [HR] 2.13, 95% confidence interval [CI] 1.18 to 3.86), and a similar VOCO risk (8.4% vs. 7.8%; adjusted HR 1.11, 95%CI 0.70-1.78) compared to those treated by conservatively. After multiple adjustment, PPG index was an independent predictor for VOCO (HR 1.30, 95% CI 1.05-1.62). The addition of PPG to the model of clinical risk factors substantially improved the predictions of VOCO (C-index 0.67 vs. 0.62, net reclassification index 0.42). CONCLUSIONS: PCI treatment was associated with improved outcomes in vessels with high PPG, but not for those with low PPG, which acquired similar risk of VOCO compared to vessels treated conservatively. QFR-derived PPG might assist the treatment strategy selection in ischemia-causing vessels.

Impact of Periprocedural Myocardial Injury and Infarction Definitions on Long-Term Mortality After Chronic Total Occlusion Percutaneous Coronary Intervention.

BACKGROUND: The prognostic implications of biomarker elevation following percutaneous coronary intervention (PCI) of chronic total occlusion (CTO) lesions remain controversial. This study assessed the association of periprocedural myocardial injury and clinically relevant definition of periprocedural myocardial infarction with subsequent outcomes after CTO-PCI. METHODS: We enrolled consecutive patients between January 2010 and December 2013 who underwent CTO-PCI at a large-volume center with serial CK-MB (creatine kinase-myocardial band) or cTnI (cardiac troponin I) measurements. The primary outcome was 5-year cardiovascular death. RESULTS: A total of 2616 patients (2691 CTOs) with postprocedural CK-MB or cTnI undergoing PCI recanalization were included, per-lesion technical success rate was 74.4%. Postprocedural CK-MB and cTnI elevation occurred in 5.6% and 65.5% patients, respectively. For 2485 patients with serial CK-MB measurements, only postprocedural peak CK-MB ≥5× upper reference limit was associated with increased 5-year cardiovascular death (adjusted hazard ratio, 9.88 [95% CI, 3.06-31.9]). In contrast, for 1233 patients with serial cTnI measurements, no such association was present in any threshold. The Society for Cardiovascular Angiography and Interventions definition of periprocedural myocardial infarction was associated with 5-year cardiovascular death (adjusted hazard ratio, 8.45 [95% CI, 3.58-20.0]), whereas the ARC-2 (Academic Research Consortium-2) and fourth UDMI (Universal Definition of Myocardial Infarction) were not. CONCLUSIONS: In a large cohort of CTO-PCI, moderate to high levels of peak postprocedural CK-MB were prognostically significant, whereas such association was not observed in postprocedural cTnI. The Society for Cardiovascular Angiography and Intervention criteria (but not ARC-2 and fourth UDMI) were identified as clinically relevant periprocedural myocardial infarction definition following CTO-PCI. Graphic Abstract: A graphic abstract is available for this article.

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.

Association of Acute Procedural Results With Long-Term Outcomes After CTO PCI.

OBJECTIVES: The aim of this study was to determine the association of procedural outcomes with long-term mortality and myocardial infarction (MI) after chronic total occlusion (CTO) percutaneous coronary intervention (PCI). BACKGROUND: The association between acute procedural results and subsequent outcomes has received limited study. METHODS: Between January 2010 and December 2013, a total of 2,659 CTO PCI patients were consecutively enrolled. Procedural results were categorized into 3 groups: 1) optimal recanalization, with reperfusion of the occluded vessel and side branches (if any) with TIMI (Thrombolysis In Myocardial Infarction) flow grade 3; 2) suboptimal recanalization, meeting any of the following criteria: persistence of significant side branch occlusion, final TIMI flow grade 1 or 2, or residual percentage diameter stenosis >30%; and 3) procedural failure (i.e., failure to cross a lesion with a balloon angioplasty catheter). The primary outcome was the 5-year composite endpoint of cardiac death and MI. RESULTS: Overall, optimal recanalization was achieved in 1,562 patients (58.7%), suboptimal recanalization was achieved in 399 patients (15.0%), and recanalization failed in 698 patients (26.3%). The 5-year incidence of the primary outcome was significantly higher in the suboptimal recanalization group compared with the optimal recanalization and the failure groups (10.1% vs. 6.5% vs. 6.3%; p = 0.046), which was driven mainly by higher risk for MI. In subgroup analysis, significant side branch occlusion was associated with numerically higher risk for 5-year MI (hazard ratio: 1.55; 95% confidence interval: 0.99 to 2.43; p = 0.054). CONCLUSIONS: In this large cohort of CTO PCI patients, suboptimal recanalization was associated with significantly higher long-term incidence of cardiac death and MI compared with optimal recanalization or procedural failure.

Orchestrated biomechanical, structural, and biochemical stimuli for engineering anisotropic meniscus.

Reconstruction of the anisotropic structure and proper function of the knee meniscus remains an important challenge to overcome, because the complexity of the zonal tissue organization in the meniscus has important roles in load bearing and shock absorption. Current tissue engineering solutions for meniscus reconstruction have failed to achieve and maintain the proper function in vivo because they have generated homogeneous tissues, leading to long-term joint degeneration. To address this challenge, we applied biomechanical and biochemical stimuli to mesenchymal stem cells seeded into a biomimetic scaffold to induce spatial regulation of fibrochondrocyte differentiation, resulting in physiological anisotropy in the engineered meniscus. Using a customized dynamic tension-compression loading system in conjunction with two growth factors, we induced zonal, layer-specific expression of type I and type II collagens with similar structure and function to those present in the native meniscus tissue. Engineered meniscus demonstrated long-term chondroprotection of the knee joint in a rabbit model. This study simultaneously applied biomechanical, biochemical, and structural cues to achieve anisotropic reconstruction of the meniscus, demonstrating the utility of anisotropic engineered meniscus for long-term knee chondroprotection in vivo.

Cell-based strategies for vascular regeneration.

Vascular regeneration is known to play an essential role in the repair of injured tissues mainly through accelerating the repair of vascular injury caused by vascular diseases, as well as the recovery of ischemic tissues. However, the clinical vascular regeneration is still challenging. Cell-based therapy is thought to be a promising strategy for vascular regeneration, since various cells have been identified to exert important influences on the process of vascular regeneration such as the enhanced endothelium formation on the surface of vascular grafts, and the induction of vessel-like network formation in the ischemic tissues. Here are a vast number of diverse cell-based strategies that have been extensively studied in vascular regeneration. These strategies can be further classified into three main categories, including cell transplantation, construction of tissue-engineered grafts, and surface modification of scaffolds. Cells used in these strategies mainly refer to terminally differentiated vascular cells, pluripotent stem cells, multipotent stem cells, and unipotent stem cells. The aim of this review is to summarize the reported research advances on the application of various cells for vascular regeneration, yielding insights into future clinical treatment for injured tissue/organ.

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.