Meng Wei

Favorable effects of resveratrol on sympathetic neural remodeling in rats following myocardial infarction.

Oxidative stress and inflammatory response induced by myocardial infarction play important roles in the development of sympathetic neural remodeling. The present study was designed to investigate whether resveratrol can improve sympathetic neural remodeling and hence cause less arrhythmias via its anti-oxidant and anti-inflammatory effects. Male Sprague Dawley rats were randomly assigned to either vehicle or resveratrol (1 mg/kg) treatment for 4 weeks post myocardial infarction. Another group of sham operated rats served as controls. Cardiac electrophysiology examination was performed to evaluate the severity of ventricular arrhythmias. Sympathetic neural remodeling characterized by heterogeneous nerve sprouting and sympathetic hyperinnervation was assessed by immunohistochemistry study. Western blotting and ELISA were used to evaluate inflammatory responses and oxidative stress was also quantified. Resveratrol treatment resulted in less episodes of inducible ventricular arrhythmias which was closely associated with attenuated sympathetic neural remodeling (P<0.001, respectively). Decreased nerve growth factor (NGF) expression was also observed in resveratrol treated rats in the peri-infarct area at 4 weeks after myocardial infarction (P<0.001). Interestingly, beneficial effects of resveratrol were also associated with less inflammatory responses and oxidative stress. Our data indicated that resveratrol can suppress sympathetic neural remodeling process after myocardial infarction via attenuated inflammatory responses and oxidative stress, which in turn leads to less inducibility of ventricular arrhythmias.

REGULATION OF NOGO-B EXPRESSION IN THE LESION OF AORTIC ANEURYSMS

1 Our previous study showed that Nogo‐B was highly expressed in endothelial cells and downregulated in endothelial cells following induction by lysophatidycholine, which contirubted to atherosclerotic lesions. However, the role of Nogo‐B in the development of aortic aneurysms remains unclear. 2 In the present study, segments of thoracic aortic aneurysms (TAA) and adjacent normal thoracic aortic tissues (NTA) without aneurysmal changes were obtained from 31 patients undergoing graft surgery. The mRNA and protein expression levels of Nogo‐B were measured with semiquantitative reverse transcription–polymerase chain reaction, western blotting and immunohistochemistry. 3 The results demonstrate that Nogo‐B mRNA expression levels in TAA lesions decreased to 45% compared with levels in NTA lesions and that protein levels in TAA decreased to 35%. Tissue Nogo immunohistochemical staining in aortic specimens suggested the involvement of Nogo in neovascularization and smooth muscle cell proliferation. The weaker brown staining of endothelial cells in TAA lesions suggested the lower expression of Nogo‐B in TAA lesions. 4 These results demonstrate that Nogo‐B mRNA and protein expression are downregulated in TAA lesions. It is concluded that the reduction of Nogo‐B protein expression in TAA lesions is closely correlated to the formation of aneurysm and that Nogo‐B may play a protective role in the pathological process of aneurysms.

Procedural success of CTO recanalization: Comparison of the J-CTO score determined by coronary CT angiography to invasive angiography

OBJECTIVESnThe J-CTO score is based on invasive angiography, combines several parameters of chronic total coronary occlusions (CTO), and is well established to predict the likelihood of success of percutaneous recanalization. The purpose of this study was to evaluate and validate a J-CTOCT score derived from coronary computed tomography angiography (coronary CTA).nnnMETHODSnBetween April 2011 and December 2014, 159 consecutive patients were retrospectively included. All had at least one CTO in invasive angiography, had coronary CTA performed at an interval of no more than one week from invasive angiography, and had an attempt at percutaneous coronary intervention (PCI) following coronary CTA In parallel to the angiographic J-CTO score, the J-CTOCT score was determined by awarding one point each for a blunt vessel stump, bending > 45°, occlusion length ≥ 20 mm, presence of calcium covering > 50% of any vessel cross-section within the occlusion, or a previously failed attempt at PCI. a. Both scores were compared regarding their ability to predict successful recanalization.nnnRESULTSnA total of 171 CTO lesions were analyzed. Intraobserver (k = 0.814, p < 0.001) and interobserver agreement (k = 0.771, p < 0.001) for calculation of the J-CTOCT score were close. The mean occlusion length measured by coronary CTA was significantly shorter than in invasive angiography (27.6 ± 14.8 mm vs. 37.2 ± 18.8 mm, p < 0.001). The J-CTOCT score (mean: 1.9 ± 1.4) correlated closely to the angiographic J-CTO score (mean: 1.8 ± 1.3, r = 0.856, p < 0.001), and in 122/171 lesions (71%), the scores were identical. Both J-CTOCT score (area under curve: 0.882, p < 0.001) and angiographic J-CTO score (area under curve: 0.868, p < 0.001) yielded similarly high predictive value for successful guidewire crossing within 30 min (p = 0.496).nnnCONCLUSIONSnWhile the length of coronary occlusions in coronary CTA is significantly shorter than in invasive angiography, a J-CTOCT score determined by coronary CTA closely correlates to the angiographic J-CTO score. .

Angiographic patterns of in-stent restenosis classified by computed tomography in patients with drug-eluting stents: correlation with invasive coronary angiography.

AbstractObjectivesTo evaluate the diagnostic accuracy of Mehran’s in-stent restenosis (ISR) classification by coronary computed angiography (CCTA), with reference to invasive coronary angiography (ICA).MethodsConsecutive symptomatic patients, who had clinically suspected ISR and implanted stent diameter ≥ 3xa0mm, were prospectively enrolled in our study. Mehran’s classification was employed by CCTA and ICA to classify ISR lesions into four subtypes: focal, diffuse intrastent, diffuse proliferative and total occlusion. CCTA and ICA measurement of lesion length was further compared.ResultsSixty-one patients with 101 implanted stents were included in our study. The overall sensitivity, specificity, PPV and NPV of CCTA diagnosis of binary ISR, as shown by patient-based analysis (nu2009=u200961), were 100xa0% (49/49), 75xa0% (8/12), 92.45xa0% (49/53) and 100xa0% (8/8) respectively. Mehran’s classification of CCTA correlated well with ICA findings. The diagnostic accuracy of CCTA for class I, class II, class III and class IV lesions was 92.5xa0%, 91.67xa0%, 100xa0% and 100xa0% respectively. Lesion length was assessed to be significantly longer with CCTA than with ICA (11.03u2009±u20095.89xa0mm versus 8.56u2009±u20094.99xa0mm, Pu2009<u20090.001).ConclusionsAngiographic patterns of in-stent restenosis can be accurately classified by coronary computed angiography. The lesion length measured by CCTA is longer than that assessed by invasive coronary angiographyKey Points• Patterns of in-stent restenosis can be accurately classified by coronary computed angiography.n • Lesion length appears longer on CCTA than on invasive coronary angiography.n • Stent occlusion is better delineated by coronary computed angiography.n • Optimal treatment can be planned pre-operatively based on CCTA evaluation.

Comparison of Myocardial Transmural Perfusion Gradient by Magnetic Resonance Imaging to Fractional Flow Reserve in Patients With Suspected Coronary Artery Disease

The goal of this study was to evaluate the diagnostic accuracy of transmural perfusion gradient (TPG) and transmural perfusion gradient reserve (TPGR) with 3.0 T cardiac magnetic resonance (CMR) against invasively determined fractional flow reserve (FFR) to detect coronary artery stenosis. Quantitative analysis of myocardial perfusion with CMR to diagnosis coronary artery disease (CAD) has been widely accepted. However, traditional transmural myocardial perfusion analysis with CMR neglects that endocardium is more vulnerable to ischemia than epicardium. TPG and TPGR can take the inhomogenous perfusion impairment into account and be more sensitive and specific for diagnosis of CAD. In this study, 71 patients (57 men, age 60.1 ± 6.4 years) with known or suspected CAD referred for invasive angiography study underwent rest and adenosine-induced stress CMR perfusion imaging scan. FFR was attempted to be measured in all major epicardial coronary arteries. FFR ≤0.75 was regarded to indicate a hemodynamic significant coronary lesion. A TPG ≤0.85 predicted significant CAD with sensitivity and specificity of 74.55% and 83.65%, respectively. Sensitivity and specificity of TPGR ≤0.81 were 90.91% and 89.94%, respectively. Area under the receiver-operating curve to detect FFR ≤0.75 was 0.86 for TPG and 0.95 for TPGR. TPGR yielded significantly better sensitivity and specificity for diagnosis of CAD than traditional myocardial blood flow, myocardial perfusion reserve, and TPG (p < 0.0001). In conclusion, TPG and TPGR analyses with MRI are capable of detecting hemodynamic stenosis of coronary artery and superior to traditional myocardial perfusion analysis. Furthermore, TPGR appears to be superior to TPG in the diagnosis of coronary artery stenosis.

Coronary stent occlusion: reverse attenuation gradient sign observed at computed tomography angiography improves diagnostic performance

AbstractObjectivesTo evaluate the incidence and diagnostic performance of reverse attenuation gradient (RAG) sign in patients with coronary stent occlusion.MethodsWe retrospectively included patients with suspected restenosis who underwent both coronary computed tomography angiography (CCTA) and invasive coronary angiography (ICA) within 2xa0weeks. Stent occlusion at CCTA was defined as (1) complete contrast filling defect of large calibre stents (at least 3xa0mm), or (2) presence of RAG sign in patients with small calibre stents (less than 3xa0mm) or (3) presence of RAG sign in patients with non-diagnostic image quality of stents. The diagnostic performance of RAG sign was further assessed by comparison to ICA results.ResultsA total of 162 patients with 231 implanted stents were included. ICA confirmed stent occlusion in 59 patients (99 stents). RAG sign was present in 59.3xa0% (35/59) of all stent occlusions. As shown by patient-based analysis, the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of our diagnostic criteria for detection of stent occlusion were 79.7xa0% (47/59), 100xa0% (103/103), 100xa0% (47/47) and 89.6xa0% (103/115) respectively. Superior diagnostic performance was confirmed by receiver operating characteristic (ROC) analysis with an area under the curve of 0.898.ConclusionsRAG sign observed at CCTA in patients with coronary stenting represents reverse collateral flow distal to stents and is highly specific to indicate stent occlusion.Key Points• RAG sign in patients with previous stents represents retrograde collateral flow.n • RAG sign in patients with previous stents indicates stent occlusion.n • RAG sign improves detection of stent occlusion in small calibre stents.

Tranilast stabilizes the accumulation and degranulation of resident mast cells while reducing cardiomyocyte apoptosis in a swine model of coronary microembolisation.

1. Coronary microembolisation (CME) is associated with progressive myocardial dysfunction, and mast cells (MC) might have an important role in myocardial apoptosis after CME. We investigated whether the MC stabilizer tranilast suppresses the accumulation and degranulation of MC while reducing cardiomyocyte apoptosis after CME.

Coronary competitive reverse flow: Imaging findings at CT angiography and correlation with invasive coronary angiography

OBJECTIVEnTo study the imaging features of coronary competitive reverse flow and incidence of a reverse attenuation gradient in coronary CT angiography (CTA) with correlation to invasive coronary angiography (ICA).nnnMETHODSnPatients who had undergone coronary CTA and ICA within 2 weeks were retrospectively identified in our database and reviewed. All cases with ICA-confirmed competitive reverse flow or chronic total occlusions (CTOs) were included for further analysis. The reverse attenuation gradient sign was defined as a reverse intraluminal opacification gradient of vessels which showed higher opacification in more distal compared with proximal segments. ICA findings were recorded and served as the reference to identify the clinical implications of this sign.nnnRESULTSnIn total, 134 patients (mean age, 68.1 ± 11.3 years; range, 38-90 years; 104 men) were included in our study. ICA revealed 11 cases of coronary competitive reverse flow and 123 cases of CTO. A reverse attenuation gradient sign was present in 9 of 11 patients (82%) with coronary competitive reverse flow and 72 of 123 (59%) chronically occluded coronary arteries. Myocardial bridges, distal collateral filling, as well as direct visualization of collateral connection were all more frequent in cases with coronary competitive reverse flow group compared with cases with a CTO.nnnCONCLUSIONSnThe reverse attenuation gradient sign distal to an upstream coronary severe stenosis indicates the presence of competitive collateral flow. Coronary CTA is able to correctly detect coronary competitive collateral flow and differentiate it from CTOs.

CT features in the early and late stages of chronic total coronary occlusions

OBJECTIVESnTo investigate the morphologic characteristics of early and late stages of chronic total coronary artery occlusions (CTO) in coronary computed tomography angiography (coronary CTA).nnnMETHODSnWe retrospectively analyzed patients who underwent coronary CTA and invasive coronary angiography and had at least one CTO with known duration. The following parameters were obtained in coronary CTA: calcification of the occluded segment; stump morphology; lesion length; remodeling index; presence of intra-occlusion linear contrast enhancement; and density of non-calcified CTO components. CT parameters were compared between patients with early (duration ≤ 12 months) and late (duration > 12 months) stage CTO.nnnRESULTSnOne-hundred and twelve patients with 124 chronically occluded coronary arteries were analyzed. Fifty nine patients had early stage CTOs (62 lesions) and 53 patients had late stage CTOs (62 lesions). Calcification was more severe in late-stage versus early CTOs (Agatston score: early stage, 27.4 ± 46.7 vs. late stage, 58.3 ± 112.4; p = 0.049). Remodeling index was lower in late-stage CTOs (early stage, 0.96 ± 0.2 vs. late stage, 0.88 ± 0.22; p = 0.034). In patients with late stage CTO, the presence of intra-occlusion linear enhancement was more likely (45.2% vs 14.5%, p < 0.001), and the density of non-calcified components was significantly higher (85.4 ± 27.2 HU vs. 65.7 ± 30.1 HU, p < 0.001). Stump morphology was not different between the two groups.nnnCONCLUSIONSnCoronary CTA reveals differences between chronic total coronary occlusions of longer and shorter duration. A long duration is associated with focal calcification and negative remodeling, as well as intra-occlusion enhancement and a higher density of non-calcified components.

Myocardial Upregulation of Cathepsin D by Ischemic Heart Disease Promotes Autophagic Flux and Protects Against Cardiac Remodeling and Heart Failure

Background Lysosomal dysfunction is implicated in human heart failure for which ischemic heart disease is the leading cause. Altered myocardial expression of CTSD (cathepsin D), a major lysosomal protease, was observed in human heart failure, but its pathophysiological significance has not been determined. Methods and Results Western blot analyses revealed an increase in the precursor but not the mature form of CTSD in myocardial samples from explanted human failing hearts with ischemic heart disease, which is recapitulated in chronic myocardial infarction produced via coronary artery ligation in Ctsd+/+ but not Ctsd+/− mice. Mice deficient of Ctsd displayed impaired myocardial autophagosome removal, reduced autophagic flux, and restrictive cardiomyopathy. After induction of myocardial infarction, weekly serial echocardiography detected earlier occurrence of left ventricle chamber dilatation, greater decreases in ejection fraction and fractional shortening, and lesser wall thickening throughout the first 4 weeks; pressure–volume relationship analyses at 4 weeks revealed greater decreases in systolic and diastolic functions, stroke work, stroke volume, and cardiac output; greater increases in the ventricular weight to body weight and the lung weight to body weight ratios and larger scar size were also detected in Ctsd+/− mice compared with Ctsd+/+ mice. Significant increases of myocardial autophagic flux detected at 1 and 4 weeks after induction of myocardial infarction in the Ctsd+/+ mice were diminished in the Ctsd+/− mice. Conclusions Myocardial CTSD upregulation induced by myocardial infarction protects against cardiac remodeling and malfunction, which is at least in part through promoting myocardial autophagic flux.