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.

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.

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.

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.

Advantages of Transradial Rotational Atherectomy versus Transfemoral Approach in Elderly Patients with Hard-Handling Calcified Coronary Lesions - A Single Center Experience.

BACKGROUND: Balloons cannot pass through severely calcified coronary lesion (SCCL), and sometimes they cannot be opened at a high pressure even if they can pass through the lesion. There are limited data on rotational atherectomy (RA) via transradial access (TRA) in this setting. The aim of this study was to evaluate in-hospital and 1-year outcomes in elderly patients with SCCL who underwent RA via TRA. METHODS: Eighty-six consecutive elderly patients with de novo SCCL who underwent RA were enrolled and divided into TRA (n = 45) and transfemoral access (TFA, n = 41) groups in this retrospective analysis from 2008 to 2013. Baseline characteristics and in-hospital and 1-year endpoints were compared between both groups. RESULTS: Compared to TFA, 6Fr guide catheters were used significantly more in the radial approach (p < 0.001). In the TRA group, the rate of burr size (1.25 mm) was higher and the mean burr size was smaller (p = 0.021) than that in the TFA group. Vascular access site complications, bed rest time and hospital stay were significantly lower in the TRA group compared with the TFA group (p = 0.029, < 0.001, < 0.001, respectively). However, there was no significant difference in major adverse cardiac events during hospitalization and after 1 year follow-up between both groups (p = 0.338, 1.000, respectively). CONCLUSIONS: TRA is a useful alternative to TFA in elderly patient with SCCL. The advantages of TRA over TFA include reduced time of bed rest and hospital stay and vascular complications at the puncture site.

[Anti-lipotoxic action of sesamin on renovascular hypertensive rats fed with a high-fat, high-sucrose diet].

This study is to observe anti-lipotoxic effect of sesamin on renovascular hypertensive rats fed with a high-fat, high-sucrose diet. Thirty-four complex model rats were induced by two-kidney, one-clip method and on high-fat and refined-carbohydrate diet for thirteen weeks. From the fifth week, intragastric administration of sesamin (120, 60 and 30 mg x kg(-1) x d(-1)) lasted for eight weeks. Blood pressure (BP), blood fat (BF), blood glucose (BG), free fatty acids (FFA), insulin (Ins), tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 were determined. Pathological changes of pancreas, perirenal fat and liver were semiquantitatively analyzed. In sesamin (120 and 60 mg x kg(-1) x d(-1)) group, it was found that there were decrease of levels of BP, BF, BG, TNF-alpha, IL-6 and FFA, improvement of insulin resistance and glucose tolerance, alleviation of body weight, humid weight of fat, liver and pancreas and their organ index, and reduction of islet cell hyperplasia and amount of lipid droplet vacuoles in lipocyte and hepatocyte. It is implied that sesamin had anti-lipotoxic effect and its mechanism may be closely associated with the amelioration of insulin resistance via reducing lipidoses in hepatocyte and inflammatory adipokines such as TNF-alpha and IL-6.

Sesamin exerts renoprotective effects by enhancing NO bioactivity in renovascular hypertensive rats fed with high-fat-sucrose diet.

In the present study, we aimed to evaluate the protective effect of sesamin on kidney damage and renal endothelial dysfunction in two-kidney, one-clip renovascular hypertensive rats fed with a high-fat-sucrose diet (2K1C rats on HFS diet). Sesamin was intragastrically administered to 2K1C rats on HFS diet for eight weeks. Then, we measured the levels of serum hydrogen peroxide (H2O2), total antioxidant capability (T-AOC), renal malonaldehyde (MDA), total-erythrocuprein (T-SOD) and glutathione peroxidase (GSH-P(X)). The expressions of endothelial nitric oxide synthase (eNOS), nitrotyrosine and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunit p47(phox) in the left and right renal cortexes were detected by Western blotting. Pathological changes in the left and right renal cortexes were observed by periodic acid-schiff staining (PAS) and Masson's staining. Treatment with sesamin (120 and 60mg/kg⁻¹·d⁻¹) in 2K1C rats on HFS diet improved renal function, corrected structural abnormalities, and attenuated renal oxidative stress. Furthermore, sesamin increased eNOS protein expression and reduced nitrotyrosine and p47phox protein expression. These results demonstrated that long-term treatment with sesamin had renoprotective effect and improved renal endothelial dysfunction via upregulation of eNOS expression and reduction of NO oxidative inactivation in both clipped and contralateral kidneys of 2K1C rats on HFS diet, and sesamin may have a favorably therapeutic value in treating chronic kidney disease in patients with hypertension and hyperlipemia.

[Protective effect of extract of Apocynum venetum on kidneys of streptozotocin-induced diabetic rats].

The aim of this study is to investigate the effects and mechanism of extract of Apocynum venetum (AV) on kidneys of streptozotocin-induced diabetic rats. Diabetes mellitus (DM) was induced in rats by intraperitoneal injection of streptozotocin (STZ). The indexes of the blood glucose, renal function and oxidative stress were observed. The DM rats were administrated with the AV for 8 weeks, the above-mentioned indexes were detected. The blood glucose level, BUN, 24 h urine protein excretion, urine volume, renal index, renal cortex's MDA level in model groups all increased significantly. Renal cortex's SOD and GSH activities decreased significantly compared with the normal control group (P < 0.05). The above-mentioned indexes were significantly improved by the AV treatment (P < 0.05). AV have protective effects on renal function of kidneys of streptozotocin-induced diabetic rats, and maybe via inhibition of the renal oxidative stress.

Sesamin improves endothelial dysfunction in renovascular hypertensive rats fed with a high-fat, high-sucrose diet.

The present study was designed to evaluate the possible in vivo protective effects of sesamin on hypertension and endothelial function in two-kidney, one-clip renovascular hypertensive rats fed with a high-fat, high-sucrose diet (2K1C rats on HFS diet). Sesamin was orally administered for 8 weeks in 2K1C rats on HFS diet. Then, the serum malondialdehyde level was determined. The protein expression of endothelial nitric oxide synthase (eNOS), nitrotyrosine and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunit p47(phox) in aortas was detected by Western blotting. Vasorelaxation response to acetylcholine and nitroprusside, and functional assessment of nitric oxide (NO) bioactivity were also determined in aortic rings. Sesamin treatment reduced systolic blood pressure, improved vasodilatation induced by acetylcholine and enhanced NO bioactivity in the thoracic aortas. These changes were associated with increased eNOS, decreased malondialdehyde content, and reduced nitrotyrosine and p47(phox) protein expression. All these results suggest that chronic treatment with sesamin reduces hypertension and improves endothelial dysfunction through upregulation of eNOS expression and reduction of NO oxidative inactivation in 2K1C rats on HFS diet.