Sex Differences in Clinical Outcomes Associated With Quantitative Flow Ratio-Guided Percutaneous Coronary Intervention.

Background: FAVOR III China (Comparison of Quantitative Flow Ratio Guided and Angiography Guided Percutaneous Intervention in Patients with Coronary Artery Disease) reported improved clinical outcomes in quantitative flow ratio (QFR) relative to angiography-guided percutaneous coronary intervention (PCI), but the clinical impact of QFR-guided PCI according to sex remains unknown. Objectives: The authors sought to compare sex differences in the 2-year clinical benefits of a QFR-guided PCI strategy and to evaluate the differences in outcomes between men and women undergoing contemporary PCI. Methods: This study involved a prespecified subgroup analysis of the FAVOR III China trial, in which women and men were randomized to a QFR-guided strategy or a standard angiography-guided strategy. Sex differences in clinical benefit of the QFR guidance were analyzed for major adverse cardiac events (MACE), a composite of all-cause death, myocardial infarction, or ischemia-driven revascularization within 2 years. Results: A total of 1,126 women and 2,699 men were eligible and the occurrence of 2-year MACE was similar between women and men (10.3% vs 10.5%; P = 0.96). Compared with an angiography-guided strategy, a QFR-guided strategy resulted in a 7.9% and 9.7% reduction in PCI rates in men and women, respectively. A QFR-guided strategy resulted in similar relative risk reductions for 2-year MACE in women (8.0% vs 12.7%; HR: 0.62; 95% CI: 0.42-0.90) and men (8.7% vs 12.4%; HR: 0.69; 95% CI: 0.54-0.87) (Pinteraction = 0.61). Furthermore, QFR values were not significantly different between men and women with various angiographic stenosis categories. Conclusions: A QFR-guided PCI strategy resulted in improved MACE in both men and women at 2 years compared with an angiography-guided PCI strategy. The FAVOR III China Study [FAVOR III China]; (NCT03656848).

Improved heart function and cardiac remodelling following sacubitril/valsartan in acute coronary syndrome with HF.

AIMS: This study sought to assess the effect of treatment of sacubitril/valsartan (S/V) on improving cardiac function and reversing cardiac remodelling in patients with acute coronary syndrome (ACS) complicated with heart failure with reduced ejection fraction after percutaneous coronary intervention (PCI). METHODS AND RESULTS: We enrolled 275 ACS patients with reduced left ventricular ejection fraction after PCI. The patients were divided into the routine and S/V groups according to the treatment drugs. The symptoms, N-terminal pro-brain natriuretic peptide (NT-proBNP) concentrations, echocardiographic parameters [left ventricular ejection fraction (LVEF), left ventricular mass index (LVMI), left ventricular end-diastolic volume index (LVEDVI), and left ventricular end-systolic volume index (LVESVI)], major adverse cardiac events (MACEs), and adverse reactions were recorded at baseline and 6 months after treatment when a clinical follow-up was performed. The S/V group was further divided into prespecified subgroups including unstable angina (UA) group, non-ST-elevation myocardial infarction (NSTEMI) group, and ST-elevation myocardial infarction (STEMI) group according to the type of ACS. We analysed the changes in LVEF, LVMI, LVEDVI, LVESVI, and NT-proBNP in both groups and evaluated the correlation between the changes in the above variables (ΔLVEF, ΔLVMI, ΔLVEDVI, ΔLVESVI, and ΔNT-proBNP). Cox regression model was used to assess the independent risk factors of MACE. Prespecified subgroup analyses were also conducted. Compared with baseline, LVEF increased significantly (P < 0.05), NT-proBNP, LVMI, and LVESVI decreased significantly in both groups after 6 months (P < 0.05), and LVEDVI decreased significantly in the S/V group (P = 0.001). In the S/V group, ΔLVEF (t = -2.745, P = 0.006), ΔNT-proBNP (P = 0.009), ΔLVEDVI (t = 4.203, P = 0.001), and ΔLVESVI (t = 3.907, P = 0.001) were significantly improved than those in the routine group. In the S/V group, ΔLVEF was negatively correlated with ΔNT-proBNP (r = -0.244, P = 0.004), ΔLVMI (r = -0.190, P = 0.028), ΔLVEDVI (r = -0.173, P = 0.045), and ΔLVESVI (r = -0.261, P = 0.002). In Cox regression model analysis, ΔLVEF {hazard ratio [HR] = 0.87 [95% confidence interval (CI) 0.80-0.95], P = 0.003}, ΔLVEDVI [HR = 1.04 (95% CI 1.01-1.06), P = 0.013], and ΔLVESVI [HR = 1.04 (95% CI 1.01-1.08), P = 0.026] were independent risk factors for MACE. Subgroup analysis showed that ΔLVEF (t = 6.290, P = 0.001), ΔLVEDVI (t = 2.581, P = 0.011), and ΔNT-proBNP (P = 0.019) in the NSTEMI group were significantly improved than those in the UA group, ΔLVEDVI in the NSTEMI group was significantly better than that in the STEMI group (t = -3.365, P = 0.001), and ΔLVEF in the STEMI group was significantly better than that in the UA group (t = -3.928, P = 0.001). There was a significant difference in the survival probability without MACE among the three groups in the analysis of the Kaplan-Meier curve (P = 0.042). The incidence of MACE in the UA group was significantly higher than that in the NSTEMI group (32.4% vs. 6.3%, P = 0.004). CONCLUSIONS: The cardiac function is improved and cardiac remodelling is reversed significantly after treatment of S/V in ACS patients with reduced left ventricular ejection fraction after PCI, and the improvement is more obvious than the routine group. There is a significant negative correlation between the change in LVEF and the changes in NT-proBNP, LVMI, LVEDVI, and LVESVI. The increase of LVEF and the decrease of LVEDVI and LVESVI are protective factors to improve the prognosis. Patients with myocardial infarction and reduced left ventricular ejection fraction might benefit more from the initiation of S/V as first-line heart failure treatment after PCI.

Intracoronary nicorandil induced hyperemia for physiological assessments in the coronary artery lesions.

Objective: Maximal hyperemia is a key element of invasive physiological examination. The aim of this study was to investigate the efficacy and safety of intracoronary (IC) nicorandil in comparison with adenosine 5'-triphosphate (ATP) intravenous (i.v.) injection for fractional flow reserve (FFR) measurement in coronary artery lesions. Materials and methods: In this study, 46 patients who had their FFR measured were enrolled, including 51 lesions. Hyperemia was induced by bolus 2 mg nicorandil and ATP (40 mg ATP + 36 ml saline, weight × 10 ml/h) for FFR measurement. The safety and efficacy of IC nicorandil were evaluated. Results: The mean FFR values measured by nicorandil and ATP were 0.810 ± 0.013 and 0.799 ± 0.099, p < 0.001, respectively. There was a strong correlation between FFR measured by nicorandil and ATP (r = 0.983, R 2 = 0.966, FFRnicorandil = 0.937 × FFRATP + 0.061). The rate of FFR ≤ 0.75 in the nicorandil and ATP groups was 31.37 vs. 35.29%, respectively (p = 0.841), the consistency rate was 96.08%; the FFR ≤ 0.8 rate was 41.18 and 43.14%, respectively (p = 0.674), and the consistency rate was 90.20%. In five lesions, the FFR value measured by nicorandil ranged between 0.79 and 0.82, indicating inconsistency according to FFR ≤ 0.8. The blood pressure changes caused by nicorandil and ATP were 12.96 ± 6.83 and 22.22 ± 11.44 mmHg (p < 0.001); the heart rate changes were 2.43 ± 1.31 and 6.52 ± 2.87 beats/min, respectively (p < 0.001); and the PR interval changes were 6.0 (1.0-11.0) and 9.0 (2.0-19.0) ms, respectively (p < 0.001). Visual analog scale (VAS) scores in the nicorandil group were all in the range 0-2, while in the ATP group were mostly in the range of 3-5. Conclusion: Intracoronary bolus of nicorandil (2 mg) infusion induces stable hyperemia, and it could be considered as an alternative drug to ATP for FFR measurement with a lower side effect profile in most patients.

[Dual-specificity Phosphatase 1 Suppresses Vascular Smooth Muscle Cell Calcification by Optical Atrophy 1-related Pathway].

Objective To investigate the effect of dual-specificity phosphatase 1/optical atrophy 1 (DUSP1/OPA1) signaling pathway on vascular smooth muscle cell (VSMC) calcification.Methods An in vitro model of VSMC calcification was induced by exposure to ß-glycerophosphate and calcium chloride.VSMC calcification was assessed by Alizarin Red S staining and calcium content by ELISA.Apoptosis was detected by TUNEL.Western blotting was employed to determine the protein levels of DUSP1,OPA1,Runt-related transcription factor 2 (Runx-2),bone morphogenetic protein 2 (BMP-2),and cysteinyl aspartate-specific proteinase-3 (Caspase-3).The effects of DUSP1 overexpression and OPA1 knockdown on cell calcification were investigated.Results Calcium chloride and ß-glycerolphosphate induced VSMC calcification and down-regulated the expression levels of DUSP1 (t=11.951,P<0.001) and OPA1 (t=8.487,P<0.001).DUSP1 overexpression promoted OPA1 expression (t=-8.921,P<0.001),attenuated VSMC calcification,reduced calcium content and apoptosis rate,and down-regulated the expression of Runx-2,BMP-2,and active Caspase-3 (all P<0.001).OPA1 knockdown increased calcium content and apoptosis rate,up-regulated the expression of Runx-2,BMP-2,and active Caspase-3,and promoted VSMC calcification (all P<0.001).Conclusion DUSP1 may inhibit the VSMC calcification through the OPA1 signaling pathway.

Feasibility and Safety of the Novel Vivolight Frequency Domain Optical Coherence Tomography System: A Multicenter Study.

OBJECTIVE: The study sought to assess the effectiveness and safety of the novel P60 Vivolight frequency-domain optical coherence tomography (OCT) system (Shenzhen Vivolight Medical Device & Technology). METHODS: A total of 90 patients were enrolled from 3 institutions. The pullbacks were performed with both the P60 Vivolight OCT system and the Ilumien Optis OCT system (Abbott Vascular). The primary endpoint was the clear stent length (CSL). Device safety was assessed by the record of serious procedure-related or postprocedure adverse events. The secondary endpoints were the average lumen area of stent, clear image length (CIL), system stability, and imaging catheter operability. RESULTS: The mean relative errors of CSL were 3.30% (95% confidence interval [CI], -0.71 to 7.31) in the full analysis set (FAS) and 0.83% (95% CI, -1.79 to 3.45) in the per-protocol set (PPS). The mean relative errors of the average lumen area of stent were 2.20% (95% CI, 0.70 to 3.80) in the FAS and 1.55% (95% CI, 0.30 to 2.80) in the PPS. No difference was observed in the percentage of obtaining >24 mm of CIL (93.18% in the P60 Vivolight group vs 95.45% in the Ilumien Optis group; P=.48). There were no serious procedure-related or postprocedure adverse events. CONCLUSIONS: The feasibility and safety of the novel Vivolight OCT system is equivalent to that of the Ilumien Optis OCT system.

Prognostic value of quantitative flow ratio measured immediately after drug-coated balloon angioplasty for in-stent restenosis.

OBJECTIVES: This study aimed to evaluate prognostic value of quantitative flow ratio (QFR) in drug-coated balloon (DCB) angioplasty for in-stent restenosis (ISR). BACKGROUND: There is a high incidence of recurrent ISR after DCB angioplasty. QFR is a novel method for fast computation of fractional flow reserve for the target vessel based on quantitative coronary angiography (QCA) and fluid dynamics algorithms. METHODS: Patients participating in the RESTORE ISR China randomized trial were enrolled and classified into the recurrent restenosis group and the non-recurrent restenosis group. The binary classifications followed the QCA standards of ISR. Clinical and angiographic characteristics of the groups were analyzed, and the QFRs before and after lesion preparation and after final DCB angioplasty were measured and compared. RESULTS: A total of 208 patients who underwent follow-up angiography were enrolled in the study, with 226 lesions measured in total. QFR value after DCB angioplasty (odds ratio [OR] 0.88; 95% confidence interval [CI] 0.83-0.93; p < .0001 for 1 mm increase), lesion length (OR: 1.08; 95% CI: 1.01-1.15; p = .017), and vessel caliber lumen diameter (OR: 0.35; 95% CI 0.13-0.89; p = .027) were independently associated with recurrent restenosis after DCB angioplasty. The optimal QFR cut-off value was determined to be 0.90 with a sensitivity of 0.94, specificity of 0.56, and accuracy of 0.79 in predicting recurrent restenosis. CONCLUSIONS: The QFR value after DCB angioplasty is a promising predictor of DES ISR.

Noninvasive Quantitative Plaque Analysis Identifies Hemodynamically Significant Coronary Arteries Disease.

OBJECTIVE: To evaluate the diagnostic performance of automated quantitative analysis by coronary computed tomography angiography (CCTA) in identifying lesion-specific hemodynamic abnormality. METHODS: A total of 132 patients (mean age, 61 y; 86 men) with 169 vessels (with 30% to 90% diameter stenosis), who successively underwent invasive coronary angiography with evaluation of fractional flow reserve (values ≤0.8 were defined as lesion-specific hemodynamic abnormalities), were analyzed by CCTA. CCTA images were quantitatively analyzed using automated software to obtain the following index: maximum diameter stenosis (MDS%); maximum area stenosis (MAS%); lesion length (LL); volume and burden (plaque volume×100 per vessel volume) of total plaque (total plaque volume [TPV], total plaque burden [TPB]), calcified plaque (calcified plaque volume [CPV], calcified plaque volume burden [CPB]), noncalcified plaque (noncalcified plaque volume [NCPV], noncalcified plaque volume burden [NCPB]), lipid plaque (lipid plaque volume [LPV], lipid plaque burden [LPB]), and fibrous plaque (fibrotic plaque volume [FPV], fibrotic plaque burden [FPB]); napkin-ring sign (NRS); remodeling index (RI); and eccentric index (EI). Logistic regression and area under the receiver operating characteristics (AUC) were used for statistical analysis. RESULTS: Fractional flow reserve ≤0.80 was found in 57 (33.73%) of the 169 vessels. Vessels with hemodynamic significance had greater MDS% (64.43%±8.69% vs. 57.33%±9.95%, P<0.001), MAS% (73.18%±8.56% vs. 64.66%±8.95%, P<0.001), and lipid plaque burden (12.75% [9.73%, 19.56%] vs. 9.41% [4.10%, 15.70%], P=0.01) compared with vessels with normal hemodynamics. In multivariable logistic regression analysis, MAS% >68% (odds ratio: 7.20, 95% confidence interval [CI]=2.89-17.91, P<0.001) and LPB >10.03% (odds ratio=4.32, 95% CI=1.36-13.66, P=0.01) were significant predictors of hemodynamic abnormalities. In predicting lesion-specific hemodynamic abnormalities, the AUC was 0.77 (95% CI=0.70-0.85) for MAS% versus 0.71 (95% CI=0.63-0.79) for MDS% (P<0.05), 0.66 (95% CI=0.58-0.74) for LPV (P<0.05), 0.66 (95% CI=0.58-0.74) for LPB (P<0.05), and 0.63 (95% CI=0.54-0.71) for TPB (P<0.05). The AUC of MAS%+LPB (0.83, 95% CI=0.76-0.89) was significantly improved compared with that of MAS% (0.77, 95% CI=0.70-0.85, P<0.05). CONCLUSIONS: Compared with MDS% and the volume burdens of plaque compositions, MAS% has a higher diagnostic accuracy for coronary hemodynamic abnormalities in the precise quantitative analysis of coronary plaques on the basis of CT. Furthermore, MAS%+LPB might improve the diagnostic accuracy beyond MAS% alone.

Safety and efficacy of intracoronary thrombolytic therapy via a new infusion catheter in patients with ST-segment elevation myocardial infarction with large thrombus burden: a pilot study.

BACKGROUND: A large intracoronary thrombus burden is associated with adverse clinical results. The optimal management of this scenario remains unknown. We aimed to determine the efficacy and safety of a new rapid infusion catheter combined with low-dose intracoronary thrombolysis in patients with ST-segment elevation myocardial infarction (STEMI) with a large thrombus burden. METHODS AND RESULTS: This pilot study included 22 patients with STEMI with a large thrombus burden. A large thrombus burden was defined as a definite thrombus with the largest dimension of at least two vessel diameters [thrombolysis in myocardial infarction (TIMI) thrombus grades 4 and 5]. All patients received primary percutaneous coronary intervention guided by the presence of recurrent chest pain or clinical myocardial ischemia evidences. All patients regained myocardial perfusion immediately after the infusion catheter crossed the thrombus. Local fibrinolysis with low-dose recombinant human prourokinase was administered continuously via the infusion catheter for 30 min. Repeat coronary angiography revealed marked thrombus resolution, with an improvement in TIMI flow from 0.14 ± 0.35 at baseline to 2.82 ± 0.40. Only one patient with postlysis thrombus grades 4-5 was observed. No major bleeding events were observed. CONCLUSIONS: In patients with STEMI presenting with a large thrombus burden, all patients regained myocardial perfusion immediately after the infusion catheter crossed over the thrombus, and low doses of intracoronary thrombolysis could significantly reduce the thrombus burden and improve the coronary flow without major bleeding.

Coronary Angiography-Derived Index of Microvascular Resistance.

A coronary angiography-derived index of microvascular resistance (caIMR) is proposed for physiological assessment of microvasular diseases in coronary circulation. The aim of the study is to assess diagnostic performance of caIMR, using wire-derived index of microvascular resistance (IMR) as the reference standard. IMR was demonstrated in 56 patients (57 vessels) with stable/unstable angina pectoris and no obstructive coronary arteries in three centers using the Certus pressure wire. Based on the aortic pressure wave and coronary angiograms from two projections, the caIMR was computed and assessed in blinded fashion against the IMR at an independent core laboratory. Diagnostic accuracy, sensitivity, specificity, positive predictive value and negative predictive value of the caIMR with a cutoff value of 25 were 84.2% (95% CI: 72.1% to 92.5%), 86.1% (95% CI: 70.5% to 95.3%), 81.0% (95% CI: 58.1% to 94.6%), 88.6% (95% CI: 76.1% to 95.0%), and 77.3% (95% CI: 59.5% to 88.7%) against the IMR with a cutoff value of 25. The receiver-operating curve had area under the curve of 0.919 and the correlation coefficient equaled to 0.746 between caIMR and wire-derived IMR. Hence, caIMR could eliminate the need of a pressure wire, reduce technical error, and potentially increase adoption of physiological assessment of microvascular diseases in patients with ischemic heart disease.

Stress Myocardial Blood Flow Ratio by Dynamic CT Perfusion Identifies Hemodynamically Significant CAD.

OBJECTIVES: The aim of this study was to evaluate the diagnostic accuracy of stress myocardial blood flow ratio (SFR), a novel parameter derived from stress dynamic computed tomographic perfusion (CTP), for the detection of hemodynamically significant coronary stenosis. BACKGROUND: A comprehensive cardiac computed tomographic protocol combining coronary computed tomographic angiography (CTA) and CTP can provide a simultaneous assessment of both coronary artery anatomy and ischemia. METHODS: Patients with chest pain scheduled for invasive angiography were prospectively enrolled in this study. Stress dynamic CTP was performed followed by coronary CTA using a second-generation dual-source computed tomographic system. At subsequent invasive angiography, fractional flow reserve was performed to identify hemodynamically significant stenosis. For each coronary territory, SFR was defined as the ratio of hyperemic myocardial blood flow (MBF) in an artery with stenosis to hyperemic MBF in a nondiseased artery. The diagnostic accuracy of SFR to identify hemodynamically significant stenosis was determined against the reference standard of invasive fractional flow reserve ≤0.80. RESULTS: A total of 82 patients (mean age 58.5 ± 10 years) with 101 vessels with either 1- or 2-vessel disease were included. By FFR, 48 (47.5%) vessels were deemed hemodynamically significant. Hyperemic MBF and SFR were lower for vessels with hemodynamically significant lesions (95.1 ± 32.4 ml/100 ml/min vs. 142.5 ± 31.2 ml/100 ml/min and 0.66 ± 0.14 vs. 0.90 ± 0.07, respectively; p < 0.01 for both). When compared with ≥50% stenosis by CTA, the specificity for detecting ischemia by SFR increased from 43% to 91%, while the sensitivity decreased from 95% to 62%. Accordingly, the positive and negative predictive values were 85% and 73%, respectively. The combination of stenosis ≥50% by CTA and SFR resulted in an area under the curve of 0.91, which was significantly higher compared with hyperemic MBF (area under the curve = 0.79; p = 0.013). CONCLUSIONS: Calculation of SFR by dynamic CTP provides a novel and accurate method to identify flow-limiting coronary stenosis.

Increased expression of ryanodine receptor type-2 during atrial fibrillation by miR-106-25 cluster independent mechanism.

Atrial fibrillation (AF), the most frequently encountered cardiac arrhythmia in the clinical setting and the foremost cause of stroke, results from a progressive decrease in atrial refractoriness. In addition, defective calcium signaling has been shown to play a central role in AF pathogenesis. Recently it was shown that the miR-106b-25 cluster is suppressed in patients with AF, which increased ryanodine receptor 2 (RyR2) expression. Expression of the miR-106b-25 cluster and RyR2 protein were determined in our institutional series of patients with AF. Hemodynamic properties, RyR2 binding, suppression of ATP2A2 (encoding ATPase sarcoplasmic/endoplasmic reticulum Ca2 + transporting 2) were also determined. We found that all patients had elevated RyR2 protein expression; however, a cohort of patients with AF had high miR-93, miR-106b, and miR-25 expression. There was no difference in hemodynamic properties, RyR2 binding, or suppression of ATP2A2 in either cohort of patients with AF when compared to patients with normal sinus rhythm (NSR). Immunoblot assay showed hyperactive Akt, S6K, and S6 kinases in patients with AF as compared to patients with NSR. Protein kinase C activation, as measured by PKC phosphorylation, was also hyperactive in patients with AF. Cumulatively, our findings show that RyR2 expression is regulated by multiple mechanisms including the miR-106b-25, and that PKC activation might provide novel clues to increased intracellular calcium levels during AF pathogenesis.

Comparison of 2 Different Drug-Coated Balloons in In-Stent Restenosis: The RESTORE ISR China Randomized Trial.

OBJECTIVES: The aim of the present study was to evaluate the angiographic efficacy, clinical safety, and effectiveness of the Restore paclitaxel-coated balloon in a randomized trial designed to enable the approval of the new device in China. BACKGROUND: Drug-coated balloon (DCB) angioplasty offers an effective treatment for in-stent restenosis. Restore is a new DCB with a SAFEPAX shellac-ammonium salt excipient that can avoid drug washing off during catheter delivery to the target lesion site. METHODS: In the noninferiority RESTORE ISR China (Compare the Efficacy and Safety of RESTORE DEB and SeQuent Please in Chinese Patient With Coronary In-stent Restenosis) trial, eligible patients with first occurrence of drug-eluting stent ISR were randomized to the Restore DCB or SeQuent Please DCB in a 1:1 ratio stratified by diabetes. Angiographic and clinical follow-up was planned at 9 months and 1 year, respectively, in all patients. The study was powered for the primary endpoint of 9-month in-segment late loss. RESULTS: Between May 2016 and July 2017, a total of 240 subjects at 12 sites were randomized to either the Restore group (n = 120) or the SeQuent Please group (n = 120). Nine-month in-segment late loss was 0.38 ± 0.50 mm with Restore versus 0.35 ± 0.47 mm with SeQuent Please; the 1-sided 97.5% upper confidence limit of the difference was 0.17 mm, achieving noninferiority of Restore compared with SeQuent Please (p for noninferiority = 0.02). Both DCBs had similar 1-year rates of target lesion failure (13.3% vs. 12.6%; p = 0.87). CONCLUSIONS: In this head-to-head randomized trial, the Restore DCB was noninferior to the SeQuent Please DCB for the primary endpoint of 9-month in-segment late loss. (Compare the Efficacy and Safety of RESTORE DEB and SeQuent Please in Chinese Patient With Coronary In-stent Restenosis; NCT02944890).

Corner Detection Based Automatic Segmentation of Bioresorbable Vascular Scaffold Struts in IVOCT Images.

Bioresorbable Vascular scaffold (BVS) is a promising type of stent in percutaneous coronary intervention. Struts apposition assessment is important to ensure the safety of implanted BVS. Currently, BVS struts apposition analysis in IVOCT images still depends on manual delineation of struts, which is labor intensive and time consuming. Automatic struts segmentation is highly desired to simplify and speed up quantitative analysis. However, it is difficult to segment struts accurately based on the contour, due to the influence of fractures inside strut and blood artifacts around strut. In this paper, a novel framework of automatic struts segmentation based on four corners is introduced, in which priori knowledge is utilized that struts have obvious feature of box-shape. Firstly, a cascaded AdaBoost classifier based on enriched haar-like features is trained to detect struts corners. Then, segmentation result can be obtained based on the four detected corners of each strut. Tested on five pullbacks consisting of 483 images with strut, our novel method achieved an average Dice's coefficient of 0.82 for strut segmentation areas. It concludes that our method can segment struts accurately and robustly. Furthermore, automatic struts malapposition analysis in clinical practice is feasible based on the segmentation results.

Automatic analysis of bioresorbable vascular scaffolds in intravascular optical coherence tomography images.

The bioresorbable vascular scaffold (BVS) is a new generation of bioresorbable scaffold (BRS) for the treatment of coronary artery disease. A potential challenge of BVS is malapposition, which may possibly lead to late stent thrombosis. It is therefore important to conduct malapposition analysis right after stenting. Since an intravascular optical coherence tomography (IVOCT) image sequence contains thousands of BVS struts, manual analysis is labor intensive and time consuming. Computer-based automatic analysis is an alternative, but faces some difficulties due to the interference of blood artifacts and the uncertainty of the struts number, position and size. In this paper, we propose a novel framework for a struts malapposition analysis that breaks down the problem into two steps. Firstly, struts are detected by a cascade classifier trained by AdaBoost and a region of interest (ROI) is determined for each strut to completely contain it. Then, strut boundaries are segmented within ROIs through dynamic programming. Based on the segmentation result, malapposition analysis is conducted automatically. Tested on 7 pullbacks labeled by an expert, our method correctly detected 91.5% of 5821 BVS struts with 12.1% false positives. The average segmentation Dice coefficient for correctly detected struts was 0.81. The time consumption for a pullback is 15 sec on average. We conclude that our method is accurate and efficient for BVS strut detection and segmentation, and enables automatic BVS malapposition analysis in IVOCT images.

A randomised comparison of healing response between the BuMA Supreme stent and the XIENCE stent at one-month and two-month follow-up: PIONEER-II OCT randomised controlled trial.

AIMS: The aim of this study was to compare the strut coverage of the XIENCE stent with that of the BuMA Supreme sirolimus-eluting cobalt-chromium stent, which has a shorter drug elution, on optical coherence tomography (OCT) one or two months after implantation. METHODS AND RESULTS: The PIONEER-II OCT trial was a multicentre, two-arm randomised trial, which comprised two cohorts: cohort-1 underwent an OCT imaging one month after coronary intervention (BuMA: 16 patients with 18 lesions, XIENCE: 15 patients with 17 lesions), whereas cohort-2 underwent OCT at two months (BuMA: 21 patients with 21 lesions, XIENCE: 23 patients with 28 lesions). The primary hypotheses were non-inferiority of the BuMA stent to the XIENCE stent in percent strut coverage at one month (cohort-1) or two months (cohort-2). In cohort-1, the BuMA stent was non-inferior to the XIENCE stent in terms of the strut coverage (83.8±10.4% for BuMA vs. 73.0±17.5% for XIENCE, pfor noninferiority <0.001), and was also significantly higher than the XIENCE (pfor superiority 0.037). In cohort-2, the BuMA stent was non-inferior to the XIENCE stent in OCT strut coverage (80.3±18.3% vs. 73.3±21.3%, pfor noninferiority 0.006, pfor superiority 0.24). Healing scores showed better healing in the BuMA stent in cohort-1 (32.36±21.59 vs. 54.88±34.65, p=0.027), whereas there was comparable healing between the BuMA and XIENCE stents in cohort-2 (39.86±37.77 vs. 53.75±42.84, p=0.25). CONCLUSIONS: The BuMA Supreme had a faster coverage than the XIENCE at one month, presumably due to faster and shorter sirolimus elution. The difference in tissue coverage became less evident at two months.

Automatic Side Branch Ostium Detection and Main Vascular Segmentation in Intravascular Optical Coherence Tomography Images.

Intravascular optical coherence tomography is the state-of-the-art imaging modality in percutaneous coronary intervention planning and evaluation, in which side branch ostium and main vascular measurements play critical roles. However, manual measurement is time consuming and labor intensive. In this paper, we propose a fully automatic method for side branch ostium detection and main vascular segmentation to make up manual deficiency. In our method, side branch ostium points are first detected and subsequently used to divide the lumen contour into side branch and main vascular regions. Based on the division, main vascular contour is then smoothly fitted for segmentation. In side branch ostium detection, our algorithm creatively converts the definition of curvature into the calculation of the signed included angles in global view, and originally applies a differential filter to highlight the feature of side branch ostium points. A total of 4618 images from 22 pullback runs were used to evaluate the performance of the presented method. The validation results of side branch detection were TPR = 82.8 $\%$, TNR = 98.7$\%$ , PPV = 86.8$\%$, NPV = 98.7$\%$. The average ostial distance error (ODE) was 0.22 mm, and the DSC of main vascular segmentation was 0.96. In conclusion, the qualitative and quantitative evaluation indicated that the presented method is effective and accurate.

Case report of a novel maneuver to facilitate wire access to the side branch in bifurcation intervention-balloon block and support technique.

BACKGROUND: Despite advancements in the devices and techniques used for percutaneous coronary intervention, side branch (SB) wiring remains highly challenging in certain complex bifurcation intervention cases. METHODS AND RESULTS: In this report, we demonstrate the efficacy and safety of the balloon block and support technique (BBST), which comprises inflation of an appropriately sized balloon 1-2 mm distal from the carina in the distal main branch to facilitate wire access to the SB. Between June 2012 and July 2017, we utilized the BBST as a bail-out strategy for six bifurcation cases with difficult SB wiring. In this report, we present in detail the oldest and the most recent of those cases to illustrate the use of the BBST. As a bail-out strategy, the BBST successfully facilitated SB wiring. No BBST-related complications were observed. CONCLUSIONS: The BBST may be an efficient and safe method for facilitating SB wiring in complex bifurcation intervention cases and could be used as a bail-out technique.

Ripk3 promotes ER stress-induced necroptosis in cardiac IR injury: A mechanism involving calcium overload/XO/ROS/mPTP pathway.

Receptor-interacting protein 3 (Ripk3)-mediated necroptosis contributes to cardiac ischaemia-reperfusion (IR) injury through poorly defined mechanisms. Our results demonstrated that Ripk3 was strongly upregulated in murine hearts subjected to IR injury and cardiomyocytes treated with LPS and H2O2. The higher level of Ripk3 was positively correlated to the infarction area expansion, cardiac dysfunction and augmented cardiomyocytes necroptosis. Function study further illustrated that upregulated Ripk3 evoked the endoplasmic reticulum (ER) stress, which was accompanied with an increase in intracellular Ca2+ level ([Ca2+]c) and xanthine oxidase (XO) expression. Activated XO raised cellular reactive oxygen species (ROS) that mediated the mitochondrial permeability transition pore (mPTP) opening and cardiomyocytes necroptosis. By comparison, genetic ablation of Ripk3 abrogated the ER stress and thus blocked the [Ca2+]c overload-XO-ROS-mPTP pathways, favouring a pro-survival state that ultimately resulted in the inhibition of cardiomyocytes necroptosis in the setting of cardiac IR injury. In summary, the present study helps to elucidate how necroptosis is mediated by ER stress, via the calcium overload /XO/ROS/mPTP opening axis.

Melatonin protected cardiac microvascular endothelial cells against oxidative stress injury via suppression of IP3R-[Ca2+]c/VDAC-[Ca2+]m axis by activation of MAPK/ERK signaling pathway.

The cardiac microvascular reperfusion injury is characterized by the microvascular endothelial cells (CMECs) oxidative damage which is responsible for the progression of cardiac dysfunction. However, few strategies are available to reverse such pathologies. This study aimed to explore the mechanism by which oxidative stress induced CMECs death and the beneficial actions of melatonin on CMECs survival, with a special focused on IP3R-[Ca2+]c/VDAC-[Ca2+]m damage axis and the MAPK/ERK survival signaling. We found that oxidative stress induced by H2O2 significantly activated cAMP response element binding protein (CREB) that enhanced IP3R and VDAC transcription and expression, leading to [Ca2+]c and [Ca2+]m overload. High concentration of [Ca2+]m suppressed ΔΨm, opened mPTP, and released cyt-c into cytoplasm where it activated mitochondria-dependent death pathway. However, melatonin could protect CMECs against oxidative stress injury via stimulation of MAPK/ERK that inactivated CREB and therefore blocked IP3R/VDAC upregulation and [Ca2+]c/[Ca2+]m overload, sustaining mitochondrial structural and function integrity and ultimately blockading mitochondrial-mediated cellular death. In summary, these findings confirmed the mechanisms by which oxidative injury induced CMECs mitochondrial-involved death and provided an attractive and effective way to enhance CMECs survival.

DUSP1 alleviates cardiac ischemia/reperfusion injury by suppressing the Mff-required mitochondrial fission and Bnip3-related mitophagy via the JNK pathways.

Mitochondrial fission and selective mitochondrial autophagy (mitophagy) form an essential axis of mitochondrial quality control that plays a critical role in the development of cardiac ischemia-reperfusion (IR) injury. However, the precise upstream molecular mechanism of fission/mitophagy remains unclear. Dual-specificity protein phosphatase1 (DUSP1) regulates cardiac metabolism, but its physiological contribution in the reperfused heart, particularly its influence on mitochondrial homeostasis, is unknown. Here, we demonstrated that cardiac DUSP1 was downregulated following acute cardiac IR injury. In vivo, compared to wild-type mice, DUSP1 transgenic mice (DUSP1TG mice) demonstrated a smaller infarcted area and the improved myocardial function. In vitro, the IR-induced DUSP1 deficiency promoted the activation of JNK which upregulated the expression of the mitochondrial fission factor (Mff). A higher expression level of Mff was associated with elevated mitochondrial fission and mitochondrial apoptosis. Additionally, the loss of DUSP1 also amplified the Bnip3 phosphorylated activation via JNK, leading to the activation of mitophagy. Increased mitophagy overtly consumed mitochondrial mass resulting into the mitochondrial metabolism disorder. However, the reintroduction of DUSP1 blunted Mff/Bnip3 activation and therefore alleviated the fatal mitochondrial fission/mitophagy by inactivating the JNK pathway, providing a survival advantage to myocardial tissue following IR stress. The results of our study suggest that DUSP1 and its downstream JNK pathway are therapeutic targets for conferring protection against IR injury by repressing Mff-mediated mitochondrial fission and Bnip3-required mitophagy.