Incidence and Outcomes of Inferior Vena Cava Filter Thrombus during Catheter-directed Thrombolysis for Proximal Deep Venous Thrombosis.

BACKGROUND: The aim of the study was to retrospectively evaluate the incidence and outcomes of inferior vena cava (IVC) filter thrombus during catheter-directed thrombolysis (CDT) for acute proximal deep venous thrombosis (DVT). METHODS: From October 2006 to June 2015, patients diagnosed with acute proximal DVT and received CDT after a retrievable IVC filter was placed were included. The incidence, treatment, and outcomes of IVC filter thrombus during CDT were recorded and analyzed. RESULTS: A total of 189 patients (91 women, 98 men; mean age, 57.6 ± 9.8 years; range, 24-85 years) were included in this study. Among the 189 cases, the DVTs involved popliteal iliofemoral veins in 54 patients, iliofemoral veins in 113 patients, and iliac veins in 22 patients, of which 18 patients had thrombus extended into the IVC. Of the 189 patients, a total of 8 (4.2%, 8 of 189) patients were identified with IVC filter thrombus during CDT. The IVC filter thrombus was detected on a median of 2 days (range, 2-4 days) of CDT therapy, including small-size (n = 6) and large-size (n = 2) filter thrombus. Of the 8 patients, CDTs were performed with a mean 7.6 ± 1.1 days (range, 6-11 days) after the presence of symptoms for the treatment of proximal DVT, and all the IVC filter thrombi were lysed during CDT for the proximal DVT. All the IVC filters were removed successfully with a mean of 12.8 ± 0.93 days from placement. There were no procedure- or thrombolysis-related major complications, and no symptomatic pulmonary embolism breakthrough was seen in any of the patients after the filter placement. CONCLUSIONS: IVC filter thrombus during CDT for the acute proximal DVT is uncommon, and all of them did not need any additional treatment.

A New Scoring System for Predicting Ventricular Arrhythmia Risk in Patients with Acute Myocardial Infarction.

Objective: In this study, a risk score for ventricular arrhythmias (VA) were evaluated for predicting the risk of ventricular arrhythmia (VA) of acute myocardial infarction (AMI) patients. Methods: Patients with AMI were divided into two sets according to whether VA occurred during hospitalization. Another cohort was enrolled for external validation. The area under the curve (AUC) of receiver operating characteristic (ROC) was calculated to evaluate the accuracy of the model. Results: A total of 1493 eligible patients with AMI were enrolled as the training set, of whom 70 (4.7%) developed VA during hospitalization. In-hospital mortality was significantly higher in the VA set than in the non-VA set (31.4% vs 2.7%, P=0.001). The independent predictors of VA in patients with AMI including Killip grade ≥3, STEMI patients, LVEF <50%, frequent premature ventricular beats, serum potassium <3.5 mmol/L, type 2 diabetes, and creatinine level. The AUC of the model for predicting VT/VF in the training set was 0.815 (95% CI: 0.763-0.866). A total of 1149 cases were enrolled from Xuzhou Center Hospital as the external validation set. The AUC of the model in the external validation set for predicting VT/VF was 0.755 (95% CI: 0.687-0.823). Calibration curves indicated a good consistency between the predicted and the observed probabilities of VA in both sets. Conclusion: We have established a clinical prediction risk score for predicting the occurrence of VA in AMI patients. The prediction score is easy to use, performs well and can be used to guide clinical practice.

Exosomes derived from mir-214-3p overexpressing mesenchymal stem cells promote myocardial repair.

AIMS: Exosomes are known as nanovesicles that are naturally secreted, playing an essential role in stem-mediated cardioprotection. This study mainly focused on investigating if exosomes derived from miR-214 overexpressing mesenchymal stem cells (MSCs) show more valid cardioprotective ability in a rat model of acute myocardial infarction (AMI) and its potential mechanisms. METHODS: Exosomes were isolated from control MSCs (Ctrl-Exo) and miR-214 overexpressing MSCs (miR-214OE-Exo) and then they were delivered to cardiomyocytes and endothelial cells in vitro under hypoxia and serum deprivation (H/SD) condition or in vivo in an acutely infarcted Sprague-Dawley rat heart. Regulated genes and signal pathways by miR-214OE-Exo treatment were explored using western blot analysis and luciferase assay. RESULTS IN VITRO: , miR-214OE-Exo enhanced migration, tube-like formation in endothelial cells. In addition, miR-214OE-Exo ameliorated the survival of cardiomyocytes under H/SD. In the rat AMI model, compared to Ctrl-Exo, miR-214OE-Exo reduced myocardial apoptosis, and therefore reduced infarct size and improved cardiac function. Besides, miR-214OE-Exo accelerated angiogenesis in peri-infarct region. Mechanistically, we identified that exosomal miR-214-3p promoted cardiac repair via targeting PTEN and activating p-AKT signal pathway. CONCLUSION: Exosomes derived from miR-214 overexpressing MSCs have greatly strengthened the therapeutic efficacy for treatment of AMI by promoting cardiomyocyte survival and endothelial cell function.

[Effects of hemoglobin level on the risk of acute kidney injury in patients with acute myocardial infarction].

OBJECTIVE: To investigate the effect of preoperative hemoglobin (Hb) level on the risk of developing acute kidney injury (AKI) after percutaneous coronary intervention (PCI) in patients with acute myocardial infarction (AMI). METHODS: A retrospective study was conducted. The hospitalized patients diagnosed with AMI who underwent PCI from May 2015 to May 2020 in the department of cardiology in the Affiliated Changzhou No.2 People's Hospital of Nanjing Medical University were enrolled. According to the serum creatinine (SCr) level before and after interventional therapy, the patients were divided into an AKI group and a non-AKI group. The difference in patients' Hb levels between the AKI and non-AKI groups was compared. Univariate and multivariate Logistic regression analyses were used to analyze the effects of Hb levels on the risk of AKI after interventional therapy in patients with AMI. Kaplan-Meier survival curve was used to evaluate the effects of Hb levels on patients with AMI in all-cause death in the hospital. RESULTS: A total of 922 AMI patients were enrolled in this study, of which 165 patients (17.9%) developed AKI. Compared with the non-AKI group, female patients in the AKI group had a higher proportion [35.8% (59/165) vs. 26.9% (204/757)], older (age: 69.78±14.56 vs. 66.61±13.44), with a lower rate of smoking [42.4% (70/165) vs. 51.7% (391/757)] and a higher prevalence of hypertension [73.3% (121/165) vs. 63.5% (481/757)], however, the patients in AKI group also had a worse cardiac function [the proportion of Killip grade 3 or above was higher: 33.9% (56/165) vs. 13.9% (105/757)], lower Hb level (g/L: 127.61±22.18 vs. 132.79±19.45), and there were less patients using angiotensin converting enzyme inhibitor/angiotensin II receptor blocker [ACEI/ARB, 60.0% (99/165) vs. 74.5% (564/757)] and more patients using diuretics [24.8% (41/165) vs. 17.7% (134/757)] in AKI group, the differences were statistically significant (all P < 0.05). Compared with non-AKI group, patients in AKI group had a longer operation time [operation time > 60 minutes: 4.2% (7/165) vs. 1.5% (11/757)] and received more contrast media during the operative procedure [contrast media > 100 mL: 16.4% (27/165) vs. 3.6% (27/757)], the individuals had a higher rate of intra-operative hypotension [16.4% (27/165) vs. 8.2% (62/757)], and more patients were implanted more than 2 stents [8.5% (14/165) vs. 3.6% (27/757), all P < 0.05]. Univariate Logistic regression analysis suggested that each 1 g/L increase in preoperative Hb level was associated with a 1.2% decrease in the risk of postoperative AKI [odds ratio (OR) = 0.988, 95% confidence interval (95%CI) was 0.980-0.996, P = 0.003]. Meanwhile, for every 1 standard deviation increase in preoperative Hb level, the risk of postoperative AKI decreased by 22.1% (OR = 0.779, 95%CI was 0.661-0.918, P = 0.003). The patients were divided into low, medium and high concentration groups according to Hb levels (Hb levels were < 110 g/L, 110-150 g/L, ≥ 150 g/L, respectively), and multivariate Logistic regression analysis showed that the risk of AKI was significantly reduced in the high concentration group compared with that in the low concentration group (OR = 0.463, 95%CI was 0.241-0.888, P = 0.020). The Kaplan-Meier survival curve analysis indicated that the short term survival after coronary intervention in AMI patients with low Hb concentration was significantly lower than that in patients with medium and high Hb concentration (Log-Rank: χ2 = 23.215, P < 0.001). CONCLUSIONS: Preoperative lower Hb level is an independent risk factor for postoperative AKI in AMI patients. AMI patients with lower Hb levels have an increased risk of all-cause mortality within 1 month after AMI.

Association of plasma free triiodothyronine levels with contrast-induced acute kidney injury and short-term survival in patients with acute myocardial infarction.

Objective: Post-treatment contrast-induced acute kidney injury (CI-AKI) is associated with poor outcomes in patients with acute myocardial infarction (AMI). A lower free triiodothyronine (FT3) level predicts a poor prognosis of AMI patients. This study evaluated the effect of plasma FT3 level in predicting CI-AKI and short-term survival among AMI patients. Methods: Coronary arteriography or percutaneous coronary intervention was performed in patients with AMI. A 1:3 propensity score (PS) was used to match patients in the CI-AKI group and the non-CI-AKI group. Results: Of 1480 patients enrolled in the study, 224 (15.1%) patients developed CI-AKI. The FT3 level was lower in CI-AKI patients than in non-CI-AKI patients (3.72 ± 0.88 pmol/L vs 4.01 ± 0.80 pmol/L, P < 0.001). Compared with those at the lowest quartile of FT3, the patients at quartiles 2-4 had a higher risk of CI-AKI respectively (P for trend = 0.005). The risk of CI-AKI increased by 17.7% as FT3 level decreased by one unit after PS-matching analysis (odds ratio: 0.823; 95% CI: 0.685-0.988, P = 0.036). After a median of 31 days of follow-up (interquartile range: 30-35 days), 78 patients died, including 72 cardiogenic deaths and 6 non-cardiogenic deaths, with more deaths in the CI-AKI group than in the non-CI-AKI group (53 vs 25, P < 0.001). Kaplan-Meier survival analysis showed that patients at a lower FT3 quartile achieved a worse survival before and after matching. Conclusion: Lower FT3 may increase the risk of CI-AKI and 1-month mortality in AMI patients.

[Development and validation of a clinical predictive model for the risk of malignant ventricular arrhythmia during hospitalization in patients with acute myocardial infarction].

OBJECTIVE: To develop and validate a clinical prediction model for the risk of malignant ventricular arrhythmia in patients with acute myocardial infarction (AMI) during hospitalization, and evaluate the effect of the prediction model. METHODS: A retrospective study was conducted. A total of 2 649 patients with AMI admitted to cardiology department of Changzhou No.2 People's Hospital of Nanjing Medical University from December 2012 to August 2020 were enrolled. The clinical characteristics including gender, age, medical history, discharge diagnosis, vital signs during hospitalization, electrocardiogram characteristics at admission, laboratory examination indexes, interventional treatment, drug usage, malignant ventricular arrhythmias [mainly included sustained ventricular tachycardia (VT), ventricular flutter or ventricular fibrillation (VF)], and death were recorded. All patients were divided into two groups according to whether VT/VF occurred during their hospitalization. Independent risk factors for VT/VF during hospitalization were evaluated by multivariate Logistic regression analysis, and a clinical prediction model was constructed. The receiver operating characteristic curve (ROC curve) was plotted, and the area under ROC curve (AUC) was calculated to evaluate the accuracy of the prediction model. RESULTS: A total of 2 649 eligible patients with AMI were enrolled, of whom 134 (5.06%) developed VT/VF during hospitalization. The in-hospital mortality rate in VT/VF group was significantly higher than that in non-VT/VF group (38.1% vs. 1.7%, P < 0.01). Compared with the non-VT/VF group, the patients in the VT/VF group with lower systolic blood pressure [SBP (mmHg, 1 mmHg = 0.133 kPa): 125.9±28.2 vs. 132.0±24.2], higher random blood glucose (mmol/L: 8.6±4.8 vs. 7.4±3.7), worse cardiac function [Killip heart function grade ≥ 3: 36.6% vs. 10.7%, left ventricular ejection fraction (LVEF) < 0.50: 56.7% vs. 33.6%, frequent premature ventricular contractions: 12.7% vs. 1.2%] and more hypokalemia (46.3% vs. 17.3%), with significant differences (all P < 0.05). Multivariate Logistic regression analysis showed that Killip classification of cardiac function ≥ 3 [odds ratio (OR) = 3.540, 95% confidence interval (95%CI) was 2.336-5.363], random blood glucose > 11.1 mmol/L (OR = 1.841, 95%CI was 1.171-2.893), LVEF < 0.50 (OR = 0.546, 95%CI was 0.374-0.797), frequent premature ventricular contractions (OR = 12.361, 95%CI was 6.077-25.144), potassium < 3.5 mmol/L (OR = 4.268, 95%CI was 2.910-6.259), SBP < 90 mmHg (OR = 0.299, 95%CI was 0.150-0.597) and creatinine (Cr) > 100 µmol/L (OR = 2.498, 95%CI was 1.170-5.334) were independent risk factors for VT/VF in patients with AMI (all P < 0.05). The clinical prediction model of VT/VF risk was constructed based on the variables selected by multivariate regression analysis. The ROC curve analysis showed that the AUC of the model in predicting VT/VF was 0.779 (95%CI was 0.735-0.823, P < 0.001); the optimal cut-off value of the model was 17, the sensitivity was 76.1%, the specificity was 67.3%. CONCLUSIONS: The incidence of VT/VF during hospitalization of AMI patients significantly increases the risk of in-hospital death. The independent risk factors of VT/VF are Killip grade ≥ 3, random blood glucose > 11.1 mmol/L, LVEF < 0.50, frequent ventricular premature beats, potassium < 3.5 mmol/L, SBP < 90 mmHg and Cr > 100 µmol/L. The newly constructed clinical prediction model has certain predictive value for the occurrence risk of VT/VF.

HIF-1α overexpression in mesenchymal stem cell-derived exosome-encapsulated arginine-glycine-aspartate (RGD) hydrogels boost therapeutic efficacy of cardiac repair after myocardial infarction.

AIMS: Naturally secreted extracellular vesicles (EVs) play important roles in stem-mediated cardioprotection. This study aimed to investigate the cardioprotective function and underlying mechanisms of EVs derived from HIF-1α engineered mesenchymal stem cells (MSCs) in a rat model of AMI. METHODS AND RESULTS: EVs isolated from HIF-1α engineered MSCs (HIF-1α-EVs) and control MSCs (NC-EVs) were prepared. In in vitro experiments, the EVs were incubated with cardiomyocytes and endothelial cells exposed to hypoxia and serum deprivation (H/SD); in in vivo experiments, the EVs were injected in the acutely infarcted hearts of Sprague-Dawley rats. Compared with NC-EVs, HIF-1α-EVs significantly inhibited the apoptosis of cardiomyocytes and enhanced angiogenesis of endothelial cells; meanwhile, HIF-1α-EVs also significantly shrunk fibrotic area and strengthened cardiac function in infarcted rats. After treatment with EVs/RGD-biotin hydrogels, we observed longer retention, higher stability in HIF-1α-EVs, and stronger cardiac function in the rats. Quantitative real-time PCR (qRT-PCR) displayed that miRNA-221-3p was highly expressed in HIF-1α-EVs. After miR-221-3p was inhibited in HIF-1α-EVs, the biological effects of HIF-1α EVs on apoptosis and angiogenesis were attenuated. CONCLUSION: EVs released by MSCs with HIF-1α overexpression can promote the angiogenesis of endothelial cells and the apoptosis of cardiomyocytes via upregulating the expression of miR-221-3p. RGD hydrogels can enhance the therapeutic efficacy of HIF-1α engineered MSCs-derived EVs.

Machine Learning to Predict Contrast-Induced Acute Kidney Injury in Patients With Acute Myocardial Infarction.

Objective: To develop predictive models for contrast induced acute kidney injury (CI-AKI) among acute myocardial infarction (AMI) patients treated invasively. Methods: Patients with AMI who underwent angiography therapy were enrolled and randomly divided into training cohort (75%) and validation cohort (25%). Machine learning algorithms were used to construct predictive models for CI-AKI. The predictive models were tested in a validation cohort. Results: A total of 1,495 patients with AMI were included. Of all the patients, 226 (15.1%) cases developed CI-AKI. In the validation cohort, Random Forest (RF) model with top 15 variables reached an area under the curve (AUC) of 0.82 (95% CI: 0.76-0.87), while the best logistic model had an AUC of 0.69 (95% CI: 0.62-0.76). ACEF (age, creatinine, and ejection fraction) model reached an AUC of 0.62 (95% CI: 0.53-0.71). RF model with top 15 variables achieved a high recall rate of 71.9% and an accuracy of 73.5% in the validation group. Random Forest model significantly outperformed logistic regression in every comparison. Conclusions: Machine learning algorithms especially Random Forest algorithm improves the accuracy of risk stratifying patients with AMI and should be used to accurately identify the risk of CI-AKI in AMI patients.

Growth differentiation factor-15 levels and the risk of contrast induced nephropathy in patients with acute myocardial infarction undergoing percutaneous coronary intervention: A retrospective observation study.

AIMS: To investigate the association between growth differentiation factor-15 (GDF-15) and contrast-induced nephropathy (CIN) in patients with acute myocardial infarction (AMI) undergoing percutaneous coronary intervention (PCI). METHODS: A total of 311 patients with AMI were studied retrospectively. All patients were divided into two groups according to the occurrence of CIN after PCI. Baseline clinical data were compared between two groups. Multivariate logistic regression analysis was used to identify the risk factors for CIN. Cox regression analysis was used to identify the association between GDF-15, CIN and short-term outcome. RESULTS: There were 80 patients in CIN group (average age was 71.60 ± 13.00 years; 67.5% male) and 231 patients in non-CIN group (average age was 63.80 ± 11.70 years; 71.9%male). The concentration of GDF-15 in CIN group was higher than that of non-CIN group (1232 ± 366.6 ng/L vs. 939.20 ± 309.6 ng/L, P <0.001). According to GDF-15 quartiles, patients were divided into four groups. Multivariate logistic model indicated that the highest quartile(Q4) was significantly associated with an increased risk of CIN compared with lower level of GDF-15 (Q1, Q2 and Q3) (OR : 3.572, 1.803-7.078, P < 0.001). Of 243 patients who could calculate the ACEF risk score, area under the curve (AUC) of GDF-15 was 0.793, 95%CI: 0.729-0.856, P < 0.001, while AUC of ACEF was 0.708, 95%CI: 0.630-0.786, P < 0.001. Using 10% and 30% as arbitrary thresholds to define patients at low, intermediate, and high risk, GDF-15 achieved a net reclassification improvement (NRI) of 0.32 (95%CI: 0.123-0.518, P = 0.001) compared with the ACEF risk score. Cox regression model showed that high concentration of GDF-15 (Q4) was significantly associated with an increased risk of all-cause mortality and major adverse clinical events (MACE) (HR: 8.434, 95%CI: 2.650-26.837, P <0.001; HR: 3.562, 95%CI: 1.658-7.652, P = 0.001) compared with low level of GDF-15 (Q1, Q2 and Q3). CIN was an independent predictor of all-cause mortality and MACE in AMI patients (HR: 3.535, 95%CI: 1.135-11.005, P = 0.029; HR: 5.154, 95%CI: 2.228-11.925, P <0.001). CONCLUSION: GDF-15 levels increased in CIN group in AMI patients underwent PCI. GDF-15 was an independent risk factor for CIN in AMI patients underwent PCI. GDF-15 level and CIN are independent risk factors for all-cause mortality and MACE in short-term follow-ups.

Growth differentiation factor-15 levels and the risk of contrast induced acute kidney injury in acute myocardial infarction patients treated invasively: A propensity-score match analysis.

BACKGROUND: Growth differentiation factor-15 (GDF-15) is an emerging biomarker for risk stratification in cardiovascular disease. Contrast-induced acute kidney injury (AKI) is an important complication in patients undergoing coronary angiography (CAG) or percutaneous coronary intervention (PCI). In this retrospectively observational study, we aimed to determine the role of GDF-15 and the risk of AKI in acute myocardial infarction (AMI) patients. METHODS: The medical records of 1195 patients with AMI were reviewed. After exclusion criteria, a total of 751 eligible patients who underwent CAG or PCI were studied. Preoperative clinical parameters including GDF-15 levels were recorded. Multivariate logistic regression analysis was used to identify the risk factors of AKI. Subsequently, to reduce a potential selection bias and to balance differences between the two groups, a propensity score-matched analysis was performed. We recorded the 30-day all-cause mortality of the total study population. Kaplan-Meier analysis was performed to identify the association between short term survival in AMI patients and GDF-15 level. RESULTS: Among 751 enrolled patients, 106 patients (14.1%) developed AKI. Patients were divided into two groups: AKI group (n = 106) and non-AKI group (n = 645). GDF-15 levels were significantly higher in AKI group compared to non-AKI group (1328.2 ± 349.7 ng/L vs. 1113.0 ± 371.3 ng/L, P <0.001). Multivariate logistic regression analyses showed GDF-15 was an independent risk factor of AKI (per 1000 ng/L increase of GDF-15, OR: 3.740, 95% CI: 1.940-7.207, P < 0.001). According to GDF-15 tertiles, patients were divided into three groups. Patients in middle (OR 2.93, 95% CI: 1.46-5.89, P = 0.003) and highest GDF-15 tertile (OR 3.72, 95% CI: 1.87-7.39, P <0.001) had higher risk of AKI compared to patients in the lowest GDF-15 tertile. The propensity score-matched group set comprised of 212 patients. Multivariate logistic regression revealed that GDF-15 is still an independent risk factor for AKI after matching (per 1000 ng/L increase of GDF-15, OR: 2.395, 95% CI: 1.020-5.626, P = 0.045). Based on the Kaplan-Meier analysis, the risk of 30-day all-cause mortality increased in higher GDF-15 tertiles log rank chi-square: 29.895, P <0.001). CONCLUSION: This suggests that preoperative plasma GDF-15 is an independent risk factor of AKI in AMI patients underwent CAG or PCI. GDF-15 and AKI are associated with poor short term survival of AMI patients.

Development and Validation of Nomogram to Predict Acute Kidney Injury in Patients with Acute Myocardial Infarction Treated Invasively.

To identify patients who are likely to develop contrast-induced acute kidney injury (CI-AKI) in patients with acute myocardial infarction (AMI), a nomogram was developed in AMI patients. Totally 920 patients with AMI were enrolled in our study. The discrimination and calibration of the model were validated. External validations were also carried out in a cohort of 386 AMI patients. Our results showed in the 920 eligible AMI patients, 114 patients (21.3%) developed CI-AKI in the derivation group (n = 534), while in the validation set (n = 386), 50 patients (13%) developed CI-AKI. CI-AKI model included the following six predictors: hemoglobin, contrast volume >100 ml, hypotension before procedure, eGFR, log BNP, and age. The area under the curve (AUC) was 0.775 (95% confidence interval [CI]: 0.732-0.819) in the derivation group and 0.715 (95% CI: 0.631-0.799) in the validation group. The Hosmer-Lemeshow test has a p value of 0.557, which confirms the model's goodness of fit. The AUC of the Mehran risk score was 0.556 (95% CI: 0.498-0.615) in the derivation group. The validated nomogram provided a useful predictive value for CI-AKI in patients with AMI.