LncRNA MALAT1-targeting antisense oligonucleotide ameliorates the AngII-induced vascular smooth muscle cell proliferation and migration via Nrf2/GPX4 antioxidant pathway.

ABSTRACT: The high level of oxidative stress induced by angiotensin II (AngII) is the main pathophysiological process that promotes the proliferation and migration of vascular smooth muscle cells (VSMCs) and induces vascular remodeling. LncRNA Metastasis-related lung adenocarcinoma transcript 1 (MALAT1) has been determined to play an important role in the modulation of oxidative stress and the development of cardiovascular diseases. Nevertheless, the function and underlying mechanism of MALAT1 in restenosis induced by hypertensive angioplasty remain unclear. AngII increased the expression of MALAT1 in VSMCs. We found that anti-sense oligonucleotide lncRNA MALAT1 (ASO-MALAT1) could inhibit AngII induced reactive oxygen species (ROS) production and VSMCs proliferation and migration by inducing the expression of glutathione peroxidase 4 (GPX4), which can be reversed by siRNA-GPX4. And GPX4 overexpression can inhibit the proliferation and migration of VSMCs induced by AngII. In addition, we found that the process by which MALAT1 knockdown induces GPX4 expression involves nuclear factor erythrocyte 2 related factor 2 (Nrf2). Overexpression of Nrf2 can increase the expression of GPX4, and down-regulation of GPX4 by ML385 (Nrf2 inhibitor) blocked the protective effect of ASO-MALAT1 on AngII-induced proliferation and migration of VSMCs. Ferrostatin-1 (Fer-1, ip 5mg/kg per day for 2 weeks), a GPX4 agonist, significantly inhibited neointimal formation in spontaneously hypertensive rat (SHR) by the inhibition of oxidative stress. In conclusion, these data imply that ASO-MALAT1 suppresses the AngII-induced oxidative stress, proliferation and migration of VSMCs by activating Nrf2/GPX4 antioxidant signaling. GPX4 may be a potential target for the therapeutic intervention of hypertensive vascular restenosis.

Predictive Value of Post-Percutaneous Coronary Intervention Quantitative Flow Ratio for Vessel-Oriented Composite Endpoint.

At present, there is a lack of indicators, which can accurately predict the post-percutaneous coronary intervention (post-PCI) vessel-oriented composite endpoint (VOCE). Recent studies showed that the post-PCI quantitative flow ratio (QFR) can predict post-PCI VOCE. PubMed, Embase, and Cochrane were searched from inception to March 27, 2022, and the cohort studies about that the post-PCI QFR predicts post-PCI VOCE were screened. Meta-analysis was performed, including 6 studies involving 4518 target vessels. The results of the studies included in this meta-analysis all showed that low post-PCI QFR was an independent risk factor for post-PCI VOCE after adjusting for other factors, HR (95% CI) ranging from 2.718 (1.347-5.486) to 6.53 (2.70-15.8). Our meta-analysis showed that the risk of post-PCI VOCE was significantly higher in the lower post-PCI QFR group than in the higher post-PCI QFR group (HR: 4.14, 95% CI: 3.00-5.70, P < 0.001, I2 = 27.9%). Post-PCI QFR has a good predictive value for post-PCI VOCE. Trial Registration. This trial is registered with CRD42022322001.

Prognostic of different glomerular filtration rate formulas in patients receiving percutaneous coronary intervention: insights from a multicenter observational cohort.

BACKGROUND: The relationships of renal dysfunction (RD) and chronic kidney disease (CKD) with prognosis have been well established among non-ST elevation acute coronary syndrome (NSTE-ACS) patients who receive percutaneous coronary intervention (PCI), but the efficacy of different estimated glomerular filtration rate (eGFR) formulas for predicting the prognosis is unknown. METHODS: The cohort originated from a retrospective data, which consecutively enrolled 8197 patients. The eGFR was calculated by the Cockcroft-Gault, Modification of Diet in Renal Disease (MDRD), CKD Epidemiology Collaboration-creatinine, CKD Epidemiology Collaboration-Cys-C, CKD Epidemiology Collaboration-Cys-C-creatinine and a modified abbreviated MDRD (c-aGFR) equations in Chinese CKD patients. Patients were excluded if the eGFR could not be obtained by one of the formulas. Patients were categorized as having normal renal function, mild RD, moderate RD, severe RD, or kidney failure to compare prognosis. The primary outcome was the in-hospital net adverse clinical events (NACE). The secondary outcomes were NACE and all-cause death during follow-up. RESULTS: In total, 2159 NSTE-ACS patients (age: 64.23 ± 10.25 years; males: 73.7%) were enrolled. 39 (1.8%) patients with in-hospital NACE were observed. During the 3.23 ± 1.55-year follow-up, 1.7% death and 4.2% NACE were observed in 1 year. The percentage of severe RD patients ranged from 15.4 to 39.2% according to different calculation formulas. A high prevalence of in-hospital NACE was observed in the severe RD groups (ranging from 8 to 14.3% for different formulas). Multiple regression analysis showed that a high eGFR is a protect factor against NACE and all-cause death regardless of the formula use. Receiver operating characteristic curves showed similar predictive performance of the c-aGFR when compared to other formulas (in-hospital NACE: AUC = 0.612, follow-up NACE: AUC = 0.622, and follow-up death: AUC = 0.711). CONCLUSIONS: Severe RD results in a high prevalence of in-hospital NACE in NSTE-ACS patients after PCI regardless of the formulas use. Different formulas have a similar ability to predict in-hospital and long-term prognosis in NSTE-ACS patients. The c-aGFR formula is the simplest and a more convenient formula for use in practice.

Random forest for prediction of contrast-induced nephropathy following coronary angiography.

The majority of prediction models for contrast-induced nephropathy (CIN) have moderate performance. Therefore, we aimed to develop a better pre-procedural prediction tool for CIN following contemporary percutaneous coronary intervention (PCI) or coronary angiography (CAG). A total of 3469 patients undergoing PCI/CAG between January 2010 and December 2013 were randomly divided into a training (n = 2428, 70%) and validation data-sets (n = 1041, 30%). Random forest full models were developed using 40 pre-procedural variables, of which 13 variables were selected for a reduced CIN model. CIN developed in 78 (3.21%) and 37 of patients (3.54%) in the training and validation datasets, respectively. In the validation dataset, the full and reduced models demonstrated improved discrimination over classic Mehran, ACEF CIN risk scores (AUC 0.842 and 0.825 over 0.762 and 0.701, respectively, all P < 0.05) and common estimated glomerular filtration rate. Compared to that for the Mehran risk score model, the full and reduced models had significantly improved fit based on the net reclassification improvement (all P < 0.001) and integrated discrimination improvement (P = 0.001, 0.028, respectively). Using the above models, 2462 (66.7%), 661, and 346 patients were categorized into low (< 1%), moderate (1% to 7%), and high (> 7%) risk groups, respectively. Our pre-procedural CIN risk prediction algorithm (http://cincalc.com) demonstrated good discriminative ability and was well calibrated when validated. Two-thirds of the patients were at low CIN risk, probably needing less peri-procedural preventive strategy; however, the discriminative ability of CIN risk requires further external validation. TRIAL REGISTRATION: ClinicalTrials.gov NCT01400295.

Erratum to simple pre-procedure risk stratification tool for contrast-induced nephropathy.

[This corrects the article DOI: 10.21037/jtd.2019.04.69.].

Simple pre-procedure risk stratification tool for contrast-induced nephropathy.

BACKGROUND: A few simple and pre-procedural risk models have been developed for predicting contrast-induced nephropathy (CIN), which allow for early administration of preventative strategies before coronary angiography (CAG). The study aims to develop and validate simple pre-procedure tools for predicting risk of CIN following CAG. METHODS: We retrospectively analyzed the data from 3,469 consecutive patients undergoing CAG, who were randomly assigned to a development dataset (n=2,313) and a validation dataset (n=1,156). CIN was defined as an increase in serum creatinine (SCr) ≥0.5 mg/dL from baseline within 72 hours after CAG. Multivariate logistic regression was applied to identify independent predictors of CIN to develop risk models. The possible predictors included age >75 years, hypotension, acute myocardial infarction (AMI), SCr ≥1.5 mg/dL, and congestive heart failure (CHF). RESULTS: The incidences of CIN were 3.20% and 3.55% in the training and validation dataset respectively. Compared to classical Mehran' and ACEF CIN risk score, the new score across the validation dataset exhibited similar discrimination and predictive ability on CIN (c-statistic: 0.829, 0.832, 0.812 respectively) and in-hospital mortality (c-statistic: 0.909, 0.937, 0.866 respectively) (all P>0.05). CONCLUSIONS: The easy-to-use pre-procedural prediction model only containing 5 factors had similar predictive ability on CIN and mortality.

Novel risk model for predicting acute adverse drug reactions following cardiac catheterization from TRUST study (The Safety and toleRability of UltraviSt in Patients Undergoing Cardiac CaTheterization).

BACKGROUND: Acute drug reactions (ADRs) are common complications of contrast administration following cardiac catheterization. Serious reactions may be life threatening. However, few risk models for predicting ADRs exist. The study aims to develop a novel tool for predicting the risk of ADRs [occurring within 1 hour in patients undergoing coronary angiography or percutaneous coronary intervention (PCI)]. METHODS: A total of 17,139 consecutive patients included in the TRUST study were randomly (2:1) assigned to a development data set (n=11,426) or a validation data set (n=5,713). Multivariate logistic regression was applied to identify independent predictors of contrast-induced nephropathy (CIN), including age, contrast dose, premedication, and prehydration. The performance of our model was assessed using the c-statistic for discrimination and the Hosmer-Lemeshow test for calibration. RESULTS: The overall incidence of ADRs was 42 (0.37%) in the development data set: 0.09% in the low-risk category (score: 0-2), 0.36% in the moderate-risk category (score: 3-4), and 1.78% in the high-risk category (score ≥5). The risk score across the subgroup of the study population exhibited good discrimination and predictive ability for ADRs (c-statistic: 0.694). Meanwhile, the calibration was also demonstrated to be accurate by the Hosmer-Lemeshow goodness-of-fit test (P=0.305). CONCLUSIONS: Our data showed that our simple risk model showed good discrimination and predictive ability of ADRs following cardiac catheterization.

Procalcitonin could be a reliable marker in differential diagnosis of post-implantation syndrome and infection after percutaneous endovascular aortic repair.

BACKGROUND: Thoracic endovascular aortic repair (TEVAR) is an emerging treatment modality, which has been rapidly embraced by clinicians treating thoracic aortic disease. However, the clinical manifestations of systemic inflammatory response after TEVAR as post-implantation syndrome (PIS) resemble the perioperative infection. This study aimed to evaluate changes and diagnostic value of procalcitonin (PCT) and other traditional inflammatory markers for infections after TEVAR. METHODS: We conducted a prospective clinical study that enrolled 162 consecutive aortic dissection cases, who underwent TEVAR in our institution between July 2011 and November 2012. The PCT, C-response protein (CRP), erythrocyte sedimentation rate (ESR) and blood routine examination were monitored before the operation and on days 1, 2, 3 and 5 after the operation. The diagnosis of infection was confirmed by the infection control committee with reference to Hospital Acquired Infection Diagnostic Criteria Assessment, released by the Ministry of Health of the People's Republic of China. RESULTS: Post endovascular repair of thoracic aorta, PCT changes significantly at different time points (χ(2) = 13.225, P = 0.021), without significant difference between the PIS group and the control group (0.24 ± 0.04 vs.0.26 ± 0.10, P = 0.804). PCT values were significantly higher in the first day after TEVAR than the preoperative levels (0.18 ± 0.03 vs. 0.11 ± 0.02, P < 0.001). Compared with PIS patients, the level of PCT, CRP, White blood cell (WBC) and neutrophil (NEU) in the infection patients elevated significantly (relatively χ(2) = 6.062, P = 0.048; χ(2) = 6.081, P = 0.048; χ(2) = 11.030, P = 0.004; χ(2) = 14.632, P = 0.001). According to the ROC analysis, the PCT levels in the first day after TEVAR (AUC = 0.785, P = 0.012) had better predictive values of infection than WBC, NEU CRP and ESR (AUC = 0.720, P = 0.040; AUC = 0.715, P = 0.045; AUC = 0.663, P = 0.274; AUC = 0.502, P = 0.991). The best predictive index was the changes of PCT between preoperative and postoperative (PCT), which possess AUC as 0.803 (P = 0.014). And PCT = 0.055 could be considered as an infection diagnosis cutoff value with a sensitivity of 83.3% and specificity 69.0%. CONCLUSIONS: PCT provides better diagnostic value of infection compared with other inflammatory markers. The potential applications of PCT in differential diagnosis of PIS and infection after percutaneous TEVAR deserve further studies.

Changes of cerebrospinal fluid pressure after thoracic endovascular aortic repair.

BACKGROUND: Decreasing the intracranial pressure has been advocated as one of the major protective strategies to prevent spinal cord ischemia after endovascular aortic repair. However, the actual changes of cerebrospinal fluid (CSF) pressure and its relation with spinal cord ischemia have been poorly understood. We performed CSF pressure measurements and provisional CSF withdrawal after thoracic endovascular aortic repair, and compared the changes of CSF pressure in high risk patients and in patients with new onset paraplegia and paraparesis. METHODS: Four hundred and nineteen patients were evaluated for the risk of spinal cord ischemia after thoracic endovascular aortic repair. Patients with identified risk factors before the procedure constituted group H and received prophylactic sequential CSF pressure measurement and CSF withdrawal. Patients who actually developed spinal cord ischemia constituted group P and received rescue CSF pressure measurements and CSF withdrawal. RESULTS: Among the 419 patients evaluated, 17 were graded as high risk. Four patients actually developed spinal cord ischemia after endovascular repair. The incidence of spinal cord ischemia in this investigation was 0.9%. The patients who actually developed spinal cord ischemia had no identified risk factors and had elevated CSF pressure, ranging from 15.4 to 30.0 mmHg. Six of the 17 patients graded as high risk had elevated CSF pressure: >20 mmHg in two patients and >15 mmHg in four patients. Sequential CSF pressure measurements and provisional withdrawal successfully decrease CSF pressure and prevented symptomatic spinal cord ischemia in high-risk patients. However, these measurements could only successfully reverse the neurologic deficit in two of the patients who actually developed spinal cord ischemia. CONCLUSIONS: Cerebrospinal fluid pressure was elevated in patients with spinal cord ischemia after thoracic endovascular aortic repair. Sequential measurements of CSF pressure and provisional withdrawal of CSF decreased CSF pressure effectively in high risk patients and provided effective prevention of spinal cord ischemia. Risk factor identification and prophylactic measurements play the key role in prevention of spinal cord ischemia after thoracic endovascular aortic repair.

Perioperative aortic dissection rupture after endovascular stent graft placement for treatment of type B dissection.

BACKGROUND: The perioperative aortic dissection (AD) rupture is a severe event after endovascular stent graft placement for treatment of type B AD. However, this life-threatening complication has not undergone systematic investigation. The aim of the study is to discuss the reasons of AD rupture after the procedure. METHODS: The medical record data of 563 Stanford type B AD patients who received thoracic endovascular repair from 2004 to December 2011 at our institution were collected and analyzed. Double entry and consistency checking were performed with Epidata software. RESULTS: Twelve patients died during the perioperation after thoracic endovascular repair, with an incidence of 2.1%, 66.6% were caused by aortic rupture and half of the aortic rupture deaths were caused by retrograde type A AD. In our study, 74% of the non-rupture surviving patients had the free-flow bare spring proximal stent implanted, compared with 100% of the aortic rupture patients (74% vs. 100%, P = 0.213). The aortic rupture patients are more likely to have ascending aortic diameters = 4 cm (62.5% vs. 9.0%, P = 0.032), involvement the aortic arch concavity (62% vs. 27%, P = 0.041) and have had multiple stents placed (P = 0.039). CONCLUSIONS: Thoracic AD endovascular repair is a safe and effective treatment option for AD with relative low in-hospital mortality. AD rupture may be more common in arch stent-graft patients with an ascending aortic diameter = 4 cm and with severe dissection that needs multi-stent placement. Attention should be paid to a proximal bare spring stent that has a higher probability of inducing an AD rupture. Post balloon dilation should be performed with serious caution, particularly for the migration during dilation.

Totally percutaneous thoracic endovascular aortic repair with the preclosing technique: a case-control study.

BACKGROUND: The conventional thoracic endovascular aortic repair (TEVAR) involves groin incisions under general or epidural anesthesia. As technology moves towards less invasive procedures, a total percutaneous approach is desirable. In this study, we describe a Preclosing technique and investigate its safety and efficacy for femoral access sites management, and evaluate its advantages as compared to those of traditional surgical cutdown approaches. METHODS: The Preclosing technique involves two or multiple 6 F Perclose Proglide devices deployed in the femoral artery before upsizing to a 20-25 F sheath. The sutures were secured to close the arteriotomy at the end of the procedure. The medical records of patients who underwent thoracic endovascular aortic repairs using the Preclosing technique between December 2009 and November 2010 (group A) were compared with those using surgical femoral cutdown from January 2008 to November 2009 (group B). Outcome measures included rates of technical success, early complications, anesthesia method, procedure time, cardiac care unit (CCU) stay, time from procedure to discharge, hospital stay, procedure expense, hospital cost. RESULTS: Between the two groups, there were no significant differences in baseline characteristics, in the endograft models or profiles. The technical success rate was 100.0% (85/85) in group A vs. 97.4% (147/151) in group B (P < 0.05). There was no access-related mortality in both groups. Compared with group B, the incidence of early complications were fewer in group A, 9.4% (8/85) vs. 22.5% (34/151) (P < 0.01). Local anesthesia with conscious sedation was used more often in group A, 68.2% (58/85) vs. 51.7% (78/151) in group B (P < 0.01). The procedure duration was shorter, (96 ± 33) minutes in group A vs. (127 ± 41) minutes in group B (P < 0.01). The length of the CCU stay, the duration from procedure to discharge, and the hospital stay were both reduced in group A, (117.3 ± 88.3) hours, (7.5 ± 5.3) days and (15.3 ± 6.8) days vs. (132.7 ± 115.5) hours, (10.5 ± 5.0) days and (19.5 ± 7.8) days in group B (P < 0.01). The procedure cost was RMB (109,000 ± 30,000) Yuan in group A vs. RMB (108,000 ± 25,000) Yuan in group B (P = NS). The hospital cost was RMB (130,000 ± 35,000) Yuan in group A vs. RMB (128,000 ± 33,000) Yuan in group B (P = NS). CONCLUSIONS: Total percutaneous TEAVR with the Preclosing technique is safe and effective with meticulous technique and appropriate patient selection. The Preclosing technique decreases access-related complications, depends less on general anesthesia and the surgeon's cooperation, saves procedure time and shortens the CCU/hospital stay. With these advantages, the use of two percutaneous closure devices increases the hospital cost only slightly.