Effect of negative remodeling of the side branch ostium on the efficacy of a two-stent strategy for distal left main bifurcation lesions: an intravascular ultrasound study.

OBJECTIVES: To investigate whether negative remodeling (NR) detected by intravascular ultrasound (IVUS) of the side branch ostium (SBO) would affect in-stent neointimal hyperplasia (NIH) at the one-year follow-up and the clinical outcome of target lesion failure (TLF) at the long-term follow-up for patients with left main bifurcation (LMb) lesions treated with a two-stent strategy. METHODS: A total of 328 patients with de novo true complex LMb lesions who underwent a 2-stent strategy of percutaneous coronary intervention (PCI) treatment guided by IVUS were enrolled in this study. We divided the study into two phases. Of all the patients, 48 patients who had complete IVUS detection pre- and post-PCI and at the 1-year follow-up were enrolled in phase I analysis, which aimed to analyze the correlation between NR and in-stent NIH at SBO at the 1-year follow-up. If the correlation was confirmed, the cutoff value of the remodeling index (RI) for predicting NIH ≥ 50% was analyzed next. The phase II analysis focused on the incidence of TLF as the primary endpoint at the 1- to 5-year follow-up for all 328 patients by grouping based on the cutoff value of RI. RESULTS: In phase I: according to the results of a binary logistic regression analysis and receiver operating characteristic (ROC) analysis, the RI cutoff value predicting percent NIH ≥ 50% was 0.85 based on the ROC curve analysis, with a sensitivity of 85.7%, a specificity of 88.3%, and an AUC of 0.893 (0.778, 1.000), P = 0.002. In phase II: the TLR rate (35.8% vs. 5.3%, P < 0.0001) was significantly higher in the several NR (sNR, defined as RI ≤ 0.85) group than in the non-sNR group. CONCLUSION: The NR of LCxO is associated with more in-stent NIH post-PCI for distal LMb lesions with a 2-stent strategy, and NR with RI ≤ 0.85 is linked to percent NIH area ≥ 50% at the 1-year follow-up and more TLF at the 5-year follow-up.

PCSK9 Inhibitor Added to High-Intensity Statin Therapy to Prevent Cardiovascular Events in Patients with Acute Coronary Syndrome after Percutaneous Coronary Intervention: A Randomized, Double- Blind, Placebo-Controlled, Multicenter SHAWN Study.

BACKGROUND: It is currently uncertain whether the combination of a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor and high-intensity statin treatment can effectively reduce cardiovascular events in patients with acute coronary syndrome (ACS) who have undergone percutaneous coronary intervention (PCI) for culprit lesions. METHODS: This study protocol describes a double-blind, randomized, placebo-controlled, multicenter study aiming to investigate the efficacy and safety of combining a PCSK9 inhibitor with high-intensity statin therapy in patients with ACS following PCI. A total of 1212 patients with ACS and multiple lesions will be enrolled and randomly assigned to receive either PCSK9 inhibitor plus high-intensity statin therapy or high-intensity statin monotherapy. The randomization process will be stratified by sites, diabetes, initial presentation and use of stable (≥4 weeks) statin treatment at presentation. PCSK 9 inhibitor or its placebo is injected within 4 hours after PCI for the culprit lesion. The primary endpoint is the composite of cardiovascular death, myocardial infarction, stroke, re-hospitalization due to ACS or heart failure, or any ischemia-driven coronary revascularization at one-year follow-up between two groups. Safety endpoints mean PCSK 9 inhibitor and statin intolerance. CONCLUSION: The SHAWN study has been specifically designed to evaluate the effectiveness and safety of adding a PCSK9 inhibitor to high-intensity statin therapy in patients who have experienced ACS following PCI. The primary objective of this study is to generate new evidence regarding the potential benefits of combining a PCSK9 inhibitor with high-intensity statin treatment in reducing cardiovascular events among these patients.

Clinical Value of the Quantitative Flow Ratio to Predict Long-term Target Vessel Failure in Patients with In-stent Restenosis after Drug-coated Balloon Angioplasty.

OBJECTIVE: The study sought to investigate the clinical predictive value of quantitative flow ratio (QFR) for the long-term target vessel failure (TVF) outcome in patients with in-stent restenosis (ISR) by using drug-coated balloon (DCB) treatment after a long-term follow-up. METHODS: This was a retrospective study. A total of 186 patients who underwent DCB angioplasty for ISR in two hospitals from March 2014 to September 2019 were enrolled. The QFR of the entire target vessel was measured offline. The primary endpoint was TVF, including target vessel-cardiac death (TV-CD), target vessel-myocardial infarction (TV-MI), and clinically driven-target vessel revascularization (CD-TVR). RESULTS: The follow-up time was 3.09±1.53 years, and 50 patients had TVF. The QFR immediately after percutaneous coronary intervention (PCI) was significantly lower in the TVF group than in the no-TVF group. Multivariable Cox regression analysis indicated that the QFR immediately after PCI was an excellent predictor for TVF after the long-term follow-up [hazard ratio (HR): 5.15×10-5 (6.13×10-8-0.043); P<0.01]. Receiver-operating characteristic (ROC) curve analysis demonstrated that the optimal cut-off value of the QFR immediately after PCI for predicting the long-term TVF was 0.925 (area under the curve: 0.886, 95% confidence interval: 0.834-0.938; sensitivity: 83.40%, specificity: 88.00; P<0.01). In addition, QFR≤0.925 post-PCI was strongly correlated with the TVF, including TV-MI and CD-TVR (P<0.01). CONCLUSION: The QFR immediately after PCI showed a high predictive value of TVF after a long-term follow-up in ISR patients who underwent DCB angioplasty. A lower QFR immediately after PCI was associated with a worse TVF outcome.

Dynamic natural components and morphological changes in nonculprit subclinical atherosclerosis in patients with acute coronary syndrome and mild chronic kidney disease at the 1-year follow-up and clinical significance at the 5-year follow-up.

INTRODUCTION: The natural outcome of coronary plaque in acute coronary syndrome (ACS) patients with chronic kidney disease (CKD) is unique, which can be analyzed quantitatively by optical flow ratio (OFR) software. METHODS: A total of 184 ACS patients with at least one nonculprit subclinical atherosclerosis (NSA) detected by optical coherence tomography (OCT) at baseline and 1-year follow-up were divided into non-CKD group (n = 106, estimated glomerular filtration rate (eGFR)> 90 mL/(min×1.73 m2)) and mild CKD group (n = 78, 60≤eGFR<90 mL/(min×1.73 m2)). Changes of normalized total atheroma volume (TAVn) of NSA was the primary endpoint at the 1-year follow-up. RESULTS: Patients with mild CKD showed more TAVn progression of NSA than non-CKD (p = 0.019) from baseline to the 1-year follow-up, which was mainly due to an increase in calcium TAVn (p<0.001). The morphological change in the maximal calcification thickness (p = 0.026) was higher and the change in the distance from the calcified surface to the contralateral coronary media membrane (ΔC-to-M) at the maximal cross-sectional calcium area was lower (p<0.001) in mild CKD group than in non-CKD group. Mild CKD had more NSA related MACEs at the 5-year follow-up than non-CKD (30.8% vs. 5.8%, p = 0.045). CONCLUSIONS: Mild CKD patients had more plaque progression of NSA which showed the increase of calcium component with more protrusion into the lumen morphologically at the 1-year follow-up and a higher corresponding incidence of NSA-related MACEs at the 5-year follow-up. TRIAL REGISTRATION: Clinical Trial registration ClinicalTrials.gov. NCT02140801. https://classic.clinicaltrials.gov/ct2/show/NCT02140801.

Morphologies and composition changes in nonculprit subclinical atherosclerosis in diabetic versus nondiabetic patients with acute coronary syndrome who underwent long-term statin therapy.

Although patients are undergoing similar lipid-lowering therapy (LLT) with statins, the outcomes of coronary plaque in diabetic mellitus (DM) and non-DM patients are different. Clinical data of 239 patients in this observational study with acute coronary syndrome was from our previous randomized trial were analyzed at 3 years, and 114 of them underwent OCT detection at baseline and the 1-year follow-up were re-anlayzed by a novel artificial intelligence imaging software for nonculprit subclinical atherosclerosis (nCSA). Normalized total atheroma volume changes (ΔTAVn) of nCSA were the primary endpoint. Plaque progression (PP) was defined as any increase in ΔTAVn. DM patients showed more PP in nCSA (ΔTAVn; 7.41 (- 2.82, 11.85) mm3 vs. - 1.12 (- 10.67, 9.15) mm3, p = 0.009) with similar reduction of low-density lipoprotein cholesterol (LDL-C) from baseline to 1-year. The main reason is that the lipid component in nCSA increases in DM patients and non-significantly decreases in non-DM patients, which leads to a significantly higher lipid TAVn (24.26 (15.05, 40.12) mm3 vs. 16.03 (6.98, 26.54) mm3, p = 0.004) in the DM group than in the non-DM group at the 1-year follow-up. DM was an independent predictor of PP in multivariate logistic regression analysis (OR = 2.731, 95% CI 1.160-6.428, p = 0.021). Major adverse cardiac events (MACEs) related to nCSA at 3 years were higher in the DM group than in the non-DM group (9.5% vs. 1.7%, p = 0.027). Despite a comparable reduction in LDL-C levels after LLT, more PP with an increase in the lipid component of nCSA and a higher incidence of MACEs at the 3-year follow-up was observed in DM patients.Trial registration: ClinicalTrials.gov. identifier: NCT02140801.

Prolonged infusion of bivalirudin after elective percutaneous coronary intervention protects against procedural myocardial injury (a COBER study)-a randomized trial.

Procedural myocardial injury (PMI), which is the most common complication of elective percutaneous coronary intervention (ePCI), is associated with future adverse cardiac events. In this randomized pilot trial, we assessed the effects of prolonged use of the anti-coagulant bivalirudin on PMI after ePCI. Patients undergoing ePCI were randomized into the following two groups: the bivalirudin use during operation group (BUDO, 0.75 mg/kg bolus plus 1.75 mg/kg/h) and the bivalirudin use during and after operation for 4 h (BUDAO, 0.75 mg/kg bolus plus 1.75 mg/kg/h). Blood samples were collected before and 24 h after ePCI (per 8 h). The primary outcome, PMI, was defined as an increase in post-ePCI cardiac troponin I (cTnI) levels of > 1 × 99th% upper reference limit (URL) when the pre-PCI cTnI was normal or a rise in cTnI of > 20% of the baseline value when it was above the 99th percentile URL, but it was stable or falling. Major PMI (MPMI) was defined as a post-ePCI cTnI increase of > 5 × 99th% URL. A total of 330 patients were included (n = 165 per group). The incidences of PMI and MPMI were not significantly higher in the BUDO group than in the BUDAO group (PMI: 115 [69.70%] vs. 102 [61.82%], P = 0.164; MPMI: 81 [49.09%] vs. 70 [42.42%], P = 0.269). However, the absolute change in cTnI levels (calculated as the peak value 24 h post-PCI minus the pre-PCI value) was notably larger in the BUDO group (0.13 [0.03, 1.95]) than in the BUDAO group (0.07 [0.01, 0.61]) (P = 0.045). Moreover, the incidence of bleeding events was similar between the two groups (BUDO: 0 [0.00%]; BUDAO: 2 [1.21%], P = 0.498). Prolonged infusion of bivalirudin for 4 h after ePCI reduces PMI severity without increasing the risk of bleeding.ClinicalTrials.gov.Number: NCT04120961, 09/10/2019.

Molecular cloning and functional analysis of Chinese bayberry MrSPL4 that enhances growth and flowering in transgenic tobacco.

Chinese bayberry (Myrica rubra) is an important tree in South China, with its fruit being of nutritional and high economic value. In this study, early ripening (ZJ), medium ripening (BQ) and late ripening (DK) varieties were used as test materials. Young leaves of ZJ, BQ and DK in the floral bud morphological differentiation periods were selected for transcriptome sequencing to excavate earliness related genes. A total of 4,538 differentially expressed genes were detected. Based on clustering analysis and comparisons with genes reportedly related to flowering in Arabidopsis thaliana, 25 homologous genes were identified. Of these, one gene named MrSPL4 was determined, with its expression down-regulated in DK but up-regulated in ZJ and BQ. MrSPL4 contained SBP domain and the target site of miR156, and its total and CDS length were 1,664 bp and 555 bp respectively. The overexpression vector of MrSPL4 (35S::35S::MrSPL4-pCambia2301-KY) was further constructed and successfully transfected into tobacco to obtain MrSPL4-positive plants. Based on the results of qRT-PCR, the relative expression of MrSPL4 was up regulated by 3,862.0-5,938.4 times. Additionally, the height of MrSPL4-positive plants was also significantly higher than that of wild-type (WT), with the bud stage occurring 12 days earlier. Altogether, this study identified an important gene -MrSPL4 in Chinese bayberry, which enhanced growth and flowering, which provided important theoretical basis for early-mature breeding of Chinese bayberry.

Preliminary study of the significance of reverberation by IVUS detection for patients with severe calcified lesions.

To explore the potential significance of the reverberation of calcification by comparing both intravascular ultrasound (IVUS) and optical coherence tomography (OCT) measurement post manual coregistration. The reverberation phenomenon is often detected by IVUS for severe calcified lesions post rotational atherectomy (RA), which is thought to be due to the glassy and smooth inner surfaces of calcifications. Because of the poor penetration of IVUS, it is impossible to measure the thickness of calcifications, and the relationship between multiple reverberations and the thickness of calcification lesions has not been reported before. A total of forty-nine patients with severe calcified coronary lesions that were detected by IVUS and OCT simultaneously were enrolled in our retrospective study. If reverberation phenomena were detected by IVUS, intravascular imaging (IVI) data (including distance between the IVUS catheter center and the inner surface of the reverberation signal, the intervals between all adjacent reverberation signals, the number of layers of reverberation in IVUS, and the thickness of the calcification in OCT) were measured at the same position and same direction (each cross-section had 4 mutually perpendicular directions) at 1-mm intervals. The correlation between each reverberation observational value and OCT data was the primary target in this retrospective study, and the correlation between reverberation and calcium crack post predilatation was analyzed in other 15 patients. Four hundred twenty-eight valid observational points were analyzed simultaneously by IVUS and OCT; among them, 300 points had a single layer of reverberation, 83 had double layers of reverberation and 42 had multiple layers (≥ 3 layers) of reverberation by IVUS detection post-RA. Multivariate logistic regression analysis showed that the number of layers of reverberation by IVUS was significantly related to the thickness of calcifications by OCT at the same point and in the same direction (p < 0.001). Single, double, and multiple layers of reverberation in IVUS correspond to median calcification thicknesses (interquartile ranges (IQRs)) of 0.620 mm (0.520-0.720), 0.950 mm (0.840-1.040) and 1.185 mm (1.068-1.373), respectively, by OCT detection. Another 100 points in other 15 patients with integrated IVUS data pre- and post-predilatation showed that only single layer of reverberation was related to calcium crack (p < 0.001). The number of layers of reverberation signal detected by IVUS is positively correlated with the thickness of calcifications measured by OCT post-RA and single layer of reverberation is correlated to calcium crack post-predilatation.

Dynamic natural morphologies and component changes in nonculprit subclinical atherosclerosis in patients with acute coronary syndrome at 1-year follow-up and clinical significance at 3-year follow-up.

BACKGROUND AND AIMS: We aimed to explore the dynamic natural morphologies and main components of nonculprit subclinical atherosclerotic changes underlying lesion regression (LR) or lesion progression (LP) in patients with acute coronary syndrome. METHODS: The primary endpoints were changes in percent atheroma volume (ΔPAV), normalized total atheroma volume (ΔTAVn) and each component in nonculprit subclinical atherosclerosis from baseline to 1 year measured by optical flow ratio (OFR) software. LR or LP was defined by an increase or decrease in PAV. Secondary endpoints included the correlation between changes in the lipid profile and ΔPAV/ΔTAVn and major adverse cardiac events (MACEs) related to nonculprit subclinical atherosclerosis at 3 years. RESULTS: This was a subgroup analysis of our previous randomized trial with a total of 161 nonculprit lesions analysed. In the LR (approximately 55.3% of the lesions) group, ΔTAVn was positively correlated only with lipid ΔTAVn (r = 0.482, p < 0.001) but not fibrous and calcium ΔTAVn, and ΔPAV was positively correlated with lipid ΔPAV (r = 0.315, p = 0.003) but not fibrous and calcium ΔPAV. The percent reduction in low-density lipoprotein cholesterol (LDL-C) was an independent predictor of LR in multivariate logistic regression analysis (OR = 3.574, 95% CI: 1.125-11.347, p = 0.031). The incidence of MACEs related to nonculprit lesions at 3 years was higher in the LP group than the LR group (9.9% vs. 2.2%, p = 0.040). CONCLUSIONS: LR of nonculprit subclinical atherosclerosis at 1-year follow-up was mainly caused by regression of the lipid component, which was correlated with the degree of LDL-C reduction and fewer MACEs at 3-year follow-up.

Post-PCI quantitative flow ratio predicts 3-year outcome after rotational atherectomy in patients with heavily calcified lesions.

BACKGROUND: The study sought to investigate the clinical predictive value of quantitative flow ratio (QFR) for the long-term outcome in patients with heavily calcified lesions who underwent percutaneous coronary intervention (PCI) following rotational atherectomy (RA). METHODS: In this retrospective study, 393 consecutive patients from 2009 to 2017 were enrolled. The QFR of the entire target vessel (QFRv) and the QFR of the stent plus 5 mm proximally and distally (in-segment) (QFRi) were measured. The primary endpoint was target lesion failure (TLF), including target lesion-cardiac death (TL-CD), target lesion-myocardial infarction (TL-MI), and clinically driven-target lesion revascularization (CD-TLR). RESULTS: A total of 224 patients with 224 calcified lesions completed the clinical follow-up, and 52 patients had TLF. There was no significant difference in QFRv post-PCI between non-TLF and TLF groups (p > .05). However, QFRi post PCI was significantly higher in the non-TLF group than in the TLF group. Multivariate Cox regression showed that QFRi post-PCI was an excellent predictor of TLF after a 3-year follow-up (HR 1.7E-8 [5.3E-11 -5.6E-6 ]; p < .01). Furthermore, receiver-operating characteristic curve analysis demonstrated that the optimal cutoff value of QFRi for predicting the long-term TLF was 0.94 (area under the curve: 0.826, 95% confidence interval: 0.756-0.895; sensitivity: 89.5%, specificity: 69.2%; p < .01). The QFRi ≤ 0.94 post-PCI was negatively associated with TLF, including TL-CD, TL-MI, and CD-TLR (p < .01). CONCLUSIONS: QFRi post-PCI showed a high predictive value for TLF for during a 3-year follow-up in patients who underwent PCI following RA; specifically, lower QFRi values post-PCI were associated with worse TLF.

Retrospective analysis of OCT on MB characteristics and 1-year follow-up of the ISR incidence after the DES implantation in patients with MB.

We used optical coherence tomography (OCT) to analyze the "half-moon" like phenomenon and its characteristics and observe 1-year follow-up of the in-stent restenosis (ISR) incidence after the drug eluted stent (DES) implantation in patients with the myocardial bridge (MB). Patients were retrospectively analyzed from January 2013 to December 2019. We used OCT to check 45 patients with MB and found a visible muscle layer (VML) around the vessel adventitia with the same or high density compared to the vessel media layer. There was not any significant difference in maximal thickness, maximal arch, and total length between the half-moon layer and the visible muscle layer groups (p > 0.05). Maximal thickness, arch, and total length of the half-moon layer were significantly positively related to VML, respectively (r = 0.962, 0.985, 0.742, p < 0.01). Of these 626 patients with MB seen by OCT, only 300 could be checked out by coronary angiography (CAG). Besides, the larger the thickness and arch of the VML around the vessel adventitia, the more severe the MB in these patients (p < 0.05). After the OCT use, there was no coronary perforation in these patients with MB covered with DES. After 1-year follow-up, ISR in MB covered with DES showed a notable difference among no MB, mild MB, moderate MB, and severe MB groups (p < 0.05), and ISR in DES aggravated with the MB severity. However, ISR in MB with and without covered with DES had no significant difference among the 4 groups (p > 0.05). OCT could evaluate MB characteristics accurately compared to IVUS and had a higher rate of detecting MB than CAG. Moreover, it is safe and effective to guide DES covering the mild MB segment in patients with severe coronary lesions detected by the OCT.

C/EBPZ modulates the differentiation and proliferation of preadipocytes.

BACKGROUND/OBJECTIVES: This study investigated the functions of CCAAT/enhancer-binding protein zeta (C/EBPZ; Gene ID: 10153) in adipose tissue. SUBJECTS/METHODS: Bioinformatics analysis were used to study the expression pattern of C/EBPZ in human adipose tissue. The expression and function of C/EBPZ in adipose tissue were further studied using chicken as animal model in vivo and in vitro. RESULTS: The human C/EBPZ transcripts were greater and more stable in subcutaneous adipose tissue than in visceral adipose tissue (P < 0.01), and they were increased with age in adipose tissue (P < 0.05). In addition, the chicken C/EBPZ transcripts (C/EBPZ /ACTB) of visceral (abdominal) adipose tissue were significantly different between fat and lean broilers and decreased with age during development (P < 0.01). RNA-seq analysis showed that the C/EBPZ overexpression associated with adipose tissue development and DNA replication in chicken preadipocytes (P < 0.05). Additionally, overexpression of chicken C/EBPZ inhibited preadipocytes differentiation and promoted preadipoytes proliferation in vitro (P < 0.05). In addition, C/EBPZ overexpression suppressed the promoter activities of PPARγ, C/EBPα, FASN and LPL, and promoted the promoter activities of GATA2 and FABP4 in chicken preadipocytes (P < 0.05). CONCLUSIONS: C/EBPZ modulated the differentiation and proliferation of preadipocytes, and it might be a new negative regulator of adipogenesis.

Amelioratory effect of neoandrographolide on myocardial ischemic-reperfusion injury by its anti-inflammatory and anti-apoptotic activities.

In the present study, we aimed to evaluate the cardioprotective effect of neoandrographolide (Neo) on myocardial ischemia/reperfusion injury (I/R) models and explore its possible mechanism. We randomly and equally divided male mice into sham-operation, I/R, and I/R + Neo groups. H9C2 cell line and primary neonatal rat cardiomyocytes were induced into the simulated I/R's status and used to further validate the Neo's role in vitro. Heart systolic function, indexes of myocardial injury (IMI), infarct size, pathological change, cell apoptosis, inflammatory cytokines, and indexes related to apoptotic and NF-κB signaling pathways were analyzed in vivo or in vitro after the Neo treatment. Compared to the I/R group, Neo significantly suppressed IMI, infarct size, inflammatory cell infiltration, cell apoptosis, inflammatory cytokines, bax, cleaved caspase-3, P-IKBa, and P-NF-κB protein expressions, and the translocation of NF-kB subunit p65 from the cytoplasm to the nucleus in vivo or in vitro. Still, ejected fraction, fractional shortening, and the bcl-2 protein expression were notably increased after the Neo treatment. Neo could be developed into a new drug for treating myocardial I/R by inhibiting myocardial inflammation and apoptosis, which was closely related to suppressing the activation of bax/bcl-2 and NF-κB signaling pathways.

Cut-off values of lesion and vessel quantitative flow ratio in de novo coronary lesion post-drug-coated balloon therapy predicting vessel restenosis at mid-term follow-up.

BACKGROUND: Drug-coated balloons (DCBs) have emerged as potential alternatives to drug-eluting stents in specific lesion subsets for de novo coronary lesions. Quantitative flow ratio (QFR) is a method based on the three-dimensional quantitative coronary angiography and contrast flow velocity during coronary angiography (CAG), obviating the need for an invasive fractional flow reserve procedural. This study aimed to assess the serial angiographic changes of de novo lesions post-DCB therapy and further explore the cut-off values of lesion and vessel QFR, which predict vessel restenosis (diameter stenosis [DS] ≥50%) at mid-term follow-up. METHODS: The data of patients who underwent DCB therapy between January 2014 and December 2019 from the multicenter hospital were retrospectively collected for QFR analysis. From their QFR performances, which were analyzed by CAG images at follow-up, we divided them into two groups: group A, showing target vessel DS ≥50%, and group B, showing target vessel DS <50%. The median follow-up time was 287 days in group A and 227 days in group B. We compared the clinical characteristics, parameters during DCB therapy, and QFR performances, which were analyzed by CAG images between the two groups, in need to explore the cut-off value of lesion/vessel QFR which can predict vessel restenosis. Student's t test was used for the comparison of normally distributed continuous data, Mann-Whitney U test for the comparison of non-normally distributed continuous data, and receiver operating characteristic (ROC) curves for the evaluation of QFR performance which can predict vessel restenosis (DS ≥50%) at mid-term follow-up using the area under the curve (AUC). RESULTS: A total of 112 patients with 112 target vessels were enrolled in this study. Group A had 41 patients, while group B had 71. Vessel QFR and lesion QFR were lower in group A than in group B post-DCB therapy, and the cut-off values of lesion QFR and vessel QFR in the ROC analysis to predict target vessel DS ≥50% post-DCB therapy were 0.905 (AUC, 0.741 [95% confidence interval, CI: 0.645, 0.837]; sensitivity, 0.817; specificity, 0.561; P < 0.001) and 0.890 (AUC, 0.796 [95% CI: 0.709, 0.882]; sensitivity, 0.746; specificity, 0.780; P < 0.001). CONCLUSIONS: The cut-off values of lesion QFR and vessel QFR can assist in predicting the angiographic changes post-DCB therapy. When lesion/vessel QFR values are <0.905/0.890 post-DCB therapy, a higher risk of vessel restenosis is potentially predicted at follow-up.

Relationship between neointimal strut bridge and jailed side-branch ostial area.

BACKGROUND: Our study analyzed the relationship between the neointimal strut bridge and jailed side-branch (SB) ostial area in patients with coronary heart disease (CHD) who had a single drug-eluting stent (DES) crossover of the left anterior descending coronary artery (LAD)/diagonal branch (D) bifurcation. PATIENTS AND METHODS: A total of 64 CHD patients with an LAD/D bifurcation treated by optical coherence tomography (OCT)-guided single-DES implantation and followed up at 1 year after primary percutaneous intervention (pPCI) were enrolled in our study. According to the two-dimensional OCT results, patients were divided into a non-neointimal bridge group (n = 44) and a neointimal bridge group (n = 20). Basic clinical, angiographic, 2D and 3D OCT, and DES results were analyzed. RESULTS: The blood lipid levels of the two groups after the 1­year follow-up were lower than the levels 1 year earlier (p < 0.05). There was a notable decrease in the SB ostial minimum lumen diameter and area directly after pPCI vs. before pPCI in both groups. The diameter stenosis directly after pPCI showed a clear increase compared with the pre-pPCI value in both groups (p < 0.05 or p < 0.01, respectively). The strut distance of the neointimal bridges in the neointimal bridge group was greater than in the non-neointimal bridge group (p < 0.05). A clearly short strut distance of the neointimal bridge was observed compared with the strut distance of the non-neointimal bridge in the neointimal bridge group (p < 0.05). A larger neointimal bridge area and a smaller SB ostial area were found in the neointimal bridge group compared with the non-neointimal bridge group (p < 0.05 or p < 0.01, respectively). CONCLUSION: A short strut distance facilitated formation of a neointimal bridge, which significantly influenced the SB ostial area after single crossover stenting of the SB orifice at the 1­year follow-up.

Ticagrelor versus clopidogrel for prevention of subclinical stent thrombosis detected by optical coherence tomography in patients with drug-eluting stent implantation-a multicenter and randomized study.

Introduction: This prospective, multicenter, randomized study was designed to analyze the benefits of ticagrelor over clopidogrel in reducing subclinical stent thrombosis (ST) in patients with coronary artery disease who underwent implantation of a second-generation drug-eluting stent (DES).Methods: About 352 patients with single de novo coronary stenosis were randomly assigne`d to either clopidogrel group (aspirin plus clopidogrel) or ticagrelor group (aspirin plus ticagrelor) after DES implantation for 1 year. Baseline clinical characteristics, blood chemistry markers, coronary artery angiography (CAG), and optical coherence tomography (OCT) were obtained during the index procedure. Data about clinic, CAG and OCT were also collected after 1 year follow-up. Intention-to-treat (ITT), per protocol set (PPS), and sensitivity analysis of subclinical ST were performed. Major factors associated with subclinical ST were analyzed by multivariable and univariable logistic regression models.Results: The incidence of subclinical ST in ticagrelor group was significantly low as compared to clopidogrel group (P < .05) at 1-year follow-up. Ticagrelor use was an independent factor in reducing subclinical ST (P < .05). The percentage of endothelial coverage, neointimal hyperplasia, malapposition, and edge dissection about stents were not different between the two groups (P > .05). Bleeding ratio was not markedly altered after ticagrelor treatment (P > .05). Not any significant differences were detected with regard to baseline clinical characteristics, CAG results, and DES between ticagrelor and clopidogrel groups (P > .05).Conclusion: In patients who underwent a second-generation DES implantation, using aspirin plus ticagrelor was associated with a significant reduction in subclinical ST. (ClinicalTrials.gov. Number: NCT02140801).

Serum biomarker analysis at the protein level on pulmonary hypertension secondary to old anterior myocardial infarction.

Pulmonary hypertension (PH) related to old anterior myocardial infarction (OAMI) always accompanies a bad prognosis, and thus, we aimed to screen serum biomarkers related to PH in OAMI patients. According to right ventricular systolic pressure, we divided mice into sham, OAMI, and PH-OAMI groups and evaluated body, heart and lung weight, heart function, pulmonary blood flow velocity, cardiac fibrotic area, and pulmonary arteriole condition. Lung and serum were under the proteomic analysis. Levels of three identified proteins were measured. Compared with sham and OAMI mice, PH-OAMI mice showed heart dysfunction, low pulmonary blood flow, high right ventricular systolic pressure, heavy heart and lung weight, large cardiac fibrotic area, and pathological pulmonary arteriole remodeling (P<0.05 or P<0.01). Haptoglobin, annexin A5, and Ig mu chain C region of lung and serum were changed significantly in PH-OAMI mice (P<0.01). Then, we collected serum and clinical data, measured three serum protein levels, and performed multivariate regression and receiver operating characteristic curve in patients (normal, OAMI, and PH-OAMI groups). Compared with normal and OAMI patients, serum levels of three proteins in PH-OAMI patients were also altered notably (P<0.01). These three proteins can predict PH in OAMI patients (P<0.01). Receiver operating characteristic curve analysis revealed haptoglobin (cut-off value: 78.295, sensitivity: 62.8%, specificity: 94.4%), annexin A5 (cut-off value: 151.925, sensitivity: 41.9%, specificity: 82.4%), and Ig mu chain C region (cut-off value: 168.885, sensitivity: 86.0%, specificity: 79.6%) (P<0.01). Three circulating serum proteins can be useful for the categorization of OAMI patients with and without PH.

Intensive statin versus low-dose statin + ezetimibe treatment for fibrous cap thickness of coronary vulnerable plaques.

BACKGROUND: Acute coronary syndromes mainly result from abrupt thrombotic occlusion caused by atherosclerotic vulnerable plaques (VPs) that suddenly rupture or erosion. Fibrous cap thickness (FCT) is a major determinant of the propensity of a VP to rupture and is recognized as a key factor. The intensive use of statins is known to have the ability to increase FCT; however, there is a risk of additional adverse effects. However, lower dose statin with ezetimibe is known to be tolerable by patients. The present study aimed to investigate the effect of intensive statin vs. low-dose stain + ezetimibe therapy on FCT, as evaluated using optical coherence tomography. METHOD: Patients who had VPs (minimum FCT <65 µm and lipid core >90°) and deferred from intervention in our single center from January 2014 to December 2018 were included in the trial. They were divided into the following two groups: intensive statin group (rosuvastatin 15-20 mg or atorvastatin 30-40 mg) and combination therapy group (rosuvastatin 5-10 mg or atorvastatin 10-20 mg + ezetimibe 10 mg). At the 12-month follow-up, we compared the change in the FCT (ΔFCT%) between the two groups and analyzed the association of ΔFCT% with risk factors. Fisher exact test was used for all categorical variables. Student's t test or Mann-Whitney U-test was used for analyzing the continuous data. The relationship between ΔFCT% and risk factors was analyzed using linear regression analysis. RESULT: Total 53 patients were finally enrolled, including 26 patients who were in the intensive statin group and 27 who were in the combination therapy group. At the 12-month follow-up, the serum levels of total cholesterol (TC), total triglyceride, low-density lipoprotein (LDL-C), hypersensitive C-reactive protein (hs-CRP), and lipoprotein-associated phospholipase A2 (Lp-PLA2) levels were reduced in both the groups. The ΔTC%, ΔLDL-C%, and ΔLp-PLA2% were decreased further in the combination therapy group. FCT was increased in both the groups (combination treatment group vs. intensive statin group: 128.89 ±â€Š7.64 vs. 110.19 ±â€Š7.00 µm, t = -9.282, P < 0.001) at the 12-month follow-up. The increase in ΔFCT% was more in the combination therapy group (123.46% ±â€Š14.05% vs. 91.14% ±â€Š11.68%, t = -9.085, P < 0.001). Based on the multivariate linear regression analysis, only the serum Lp-PLA2 at the 12-month follow-up (B = -0.203, t = -2.701, P = 0.010), ΔTC% (B = -0.573, t = -2.048, P = 0.046), and Δhs-CRP% (B = -0.302, t = -2.963, P = 0.005) showed an independent association with ΔFCT%. CONCLUSIONS: Low-dose statin combined with ezetimibe therapy maybe provide a profound and significant increase in FCT as compared to intensive statin monotherapy. The reductions in Lp-PLA2, ΔTC%, and Δhs-CRP% are independently associated with an increase in FCT.

Outcomes in Patients Fully Covered With Coronary Artery Aneurysm and Stenosis Lesion by Second Generation Drug-Eluting Stents After 1 Year.

We evaluated the safety and efficacy of second-generation drug-eluting stents (DES) fully covering a coronary artery aneurysm (CAA) and stenosis lesion. Patients (n = 33) with CAA and stenosis lesion (>60%) were enrolled between January 2014 and December 2017. Baseline characteristics and biochemical variables were recorded during hospital admission. Changes in CAA resolution (the reduction on CAA size), minimal lumen diameter (MLD), and diameter stenosis (DS) were determined before, just after, and 1 year after percutaneous coronary intervention (PCI). After DES implantation, MLD and DS after PCI were improved compared with those before PCI (P < .01). Also, thrombolysis in myocardial infarction blood flow was significantly enhanced after PCI (P < .01). One year after PCI, maximal CAA diameter in patients with CAA and stenosis lesion was significantly reduced compared with those just after PCI (P < .01). Meanwhile, CAA resolution ratio in these patients were more than those just after PCI (P < .01). Furthermore, there was a significant reduction about CAA length in these patients (P < .01). Last, there were no clinical events (including cardiac death, myocardial infarction, and revascularization) in the study. Second-generation DES implantation fully covering CAA and stenosis lesion was safe and effective.

Zinc finger protein 91 loss induces cardiac hypertrophy through adenosine A1 receptor down-regulation under pressure overload status.

The function of zfp91 is mainly studied in vitro, but there is no study in vivo. Accumulative data suggest that zfp91 may be an important gene to regulate all aspects of human response. However, there are no data to date about the function of zfp91 on cardiac homeostasis. Thus, we aimed to observe the role of zfp91 gene in mouse cardiomyocytes on myocardial homeostasis and related mechanisms under pressure overload. In the study, zfp91 mRNA and protein levels were significantly reduced in TAC-operated WT mice as compared with controls. Genetic ablation of zfp91 dramatically led to pathological cardiac dysfunction and hypertrophy after transverse aortic constriction (TAC). Adenosine A1 receptor (Adora1) mRNA and protein expressions were significantly down-regulated in the heart of zfp91-deletion mice with TAC. Zfp91 overexpression reversed isoproterenol-induced cardiomyocyte hypertrophy, which was abolished by selective Adora1 antagonist. Dual-luciferase reporter and ChIP-qPCR assays indicated that zfp91 acted on Adora1 promoter through its binding site. Last, Adora1 agonist rescued heart dysfunction and cardiac hypertrophy in zfp91 loss mice after TAC. Zfp91 may transcriptionally regulate Adora1 expression in the heart, which mainly maintained cardiac homeostasis under pressure overload status. It will provide a new approach to treat cardiac hypertrophy.