Association between Coronary Artery Disease Reporting and Data System-recommended Post-Coronary CT Angiography Management and Clinical Outcomes in Patients with Stable Chest Pain from a Chinese Registry.

Background Coronary Artery Disease Reporting and Data System (CAD-RADS) was developed to standardize and optimize disease management in patients after coronary CT angiography (CCTA), but the impact of CAD-RADS management recommendations on clinical outcomes remains unclear. Purpose To retrospectively assess the association between the appropriateness of post-CCTA management according to CAD-RADS version 2.0 and clinical outcomes. Materials and Methods From January 2016 to January 2018, consecutive participants with stable chest pain referred for CCTA were prospectively included in a Chinese registry and followed for 4 years. Retrospectively, CAD-RADS 2.0 classification and the appropriateness of post-CCTA management were determined. Propensity score matching (PSM) was used to adjust for confounding variables. Hazard ratios (HRs) for a major adverse cardiovascular event (MACE), relative risks for invasive coronary angiography (ICA), and the corresponding number needed to treat were estimated. Results Of the 14 232 included participants (mean age, 61 years ± 13 [SD]; 8852 male), 2330, 2756, and 2614 were retrospectively categorized in CAD-RADS 1, 2, and 3, respectively. Only 26% of participants with CAD-RADS 1-2 disease and 20% with CAD-RADS 3 received appropriate post-CCTA management. After PSM, appropriate post-CCTA management was associated with lower risk of MACEs (HR, 0.34; 95% CI: 0.22, 0.51; P < .001), corresponding to a number needed to treat of 21 in CAD-RADS 1-2 but not CAD-RADS 3 (HR, 0.86; 95% CI: 0.49, 1.85; P = .42). Appropriate post-CCTA management was associated with decreased use of ICA in CAD-RADS 1-2 (relative risk, 0.40; 95% CI: 0.29, 0.55; P < .001) and 3 (relative risk, 0.33; 95% CI: 0.28, 0.39; P < .001), resulting in a number needed to treat of 14 and 2, respectively. Conclusion In this retrospective secondary analysis, appropriate disease management after CCTA according to CAD-RADS 2.0 was associated with lower risk of MACEs and more prudent use of ICA. ClinicalTrials.gov registration no. NCT04691037 © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Leipsic and Tzimas in this issue.

The adipose-derived stem cell peptide ADSCP2 alleviates hypertrophic scar fibrosis via binding with pyruvate carboxylase and remodeling the metabolic landscape.

AIM: The purpose of this study was to investigate the function and mechanism of a novel peptide derived from adipose-derived stem cell-conditioned medium (ADSC-CM). METHODS: Mass spectrometry was applied to identify expressed peptides in ADSC-CM obtained at different time points. The cell counting kit-8 assay and quantitative reverse transcription polymerase chain reactions were performed to screen the functional peptides contained within ADSC-CM. RNA-seq, western blot, a back skin excisional model of BALB/c mice, the peptide pull-down assay, rescue experiments, untargeted metabolomics, and mixOmics analysis were performed to thoroughly understand the functional mechanism of selected peptide. RESULTS: A total of 93, 827, 1108, and 631 peptides were identified in ADSC-CM at 0, 24, 48, and 72 h of conditioning, respectively. A peptide named ADSCP2 (DENREKVNDQAKL) derived from ADSC-CM inhibited collagen and ACTA2 mRNAs in hypertrophic scar fibroblasts. Moreover, ADSCP2 facilitated wound healing and attenuated collagen deposition in a mouse model. ADSCP2 bound with the pyruvate carboxylase (PC) protein and inhibited PC protein expression. Overexpressing PC rescued the reduction in collagen and ACTA2 mRNAs caused by ADSCP2. Untargeted metabolomics identified 258 and 447 differential metabolites in the negative and positive mode, respectively, in the ADSCP2-treated group. The mixOmics analysis, which integrated RNA-seq and untargeted metabolomics data, provided a more holistic view of the functions of ADSCP2. CONCLUSION: Overall, a novel peptide derived from ADSC-CM, named ADSCP2, attenuated hypertrophic scar fibrosis in vitro and in vivo, and the novel peptide ADSCP2 might be a promising drug candidate for clinical scar therapy.

Peptide deregulated in hypertrophic scar-1 alleviates hypertrophic scar fibrosis by targeting focal adhesion kinase and pyruvate kinase M2 and remodeling the metabolic landscape.

Hypertrophic scarring is a fibrotic skin disease characterized by excessive deposition of collagens. Emerging evidence has suggested important roles for peptides in fibrosis-related diseases. Here, we demonstrate that a skin-derived endogenous peptide, peptide deregulated in hypertrophic scar-1 (PDHS1), with the sequence IATTTASAATAAAIGATPRAK, inhibits cell proliferation, promotes apoptosis, decreases the proportion of cells in S phase, and decreases collagen synthesis in hypertrophic scar fibroblasts. Additionally, treatment with PDHPS1 alleviates hypertrophic scarring in a rabbit ear model. PDHPS1 was found to bind to focal adhesion kinase (FAK) and to decrease its activity. PDHPS1 was also shown to bind to pyruvate kinase M2 (PKM2) and to decreased its expression. Smad2 phosphorylation is also inhibited by treatment with PDHPS1. Overexpression of FAK rescues the decreased expression of COL3A1 induced by PDHPS1 treatment. Targeted metabolomics revealed that PDHPS1 reprogramed metabolism that related to amino acid synthesis, leading to decreases of the key glycolysis intermediates glucose-6-phosphate and fructose-6-phosphate. These results demonstrated that the endogenous peptide PDHPS1 alleviates hypertrophic scar fibrosis in vitro and in vivo by targeting FAK and PKM2 and remodeling the metabolic landscape. Overall, treatment with PDHPS1 is a potential therapeutic strategy for hypertrophic scarring.

Catheter ablation of idiopathic left fascicular ventricular tachycardia: Implications of false tendons for mapping and ablation.

INTRODUCTION: The anatomical substrate for idiopathic left ventricular tachycardia (ILVT) remains speculative. Purkinje networks surrounding false tendons (FTs) might be involved in the reentrant circuit of ILVT. The objective was to evaluate the anatomical and electrophysiological features of false tendons FTs in relation to ILVT. METHODS: Intracardiac echocardiography (ICE) was conducted on patients with ILVT. The relationship of the FTs with ILVT was determined using electro-anatomical mapping. RESULTS: Electrophysiological evaluation and radiofrequency ablation were conducted in 23 consecutive patients with ILVT. FTs were identified in 19/23 cases (82.6%) with P1 potentials during VT recorded at the FT in 14 of these patients (73.7%). Three FT types were identified. In type 1, the FT attached the septum to the base of the posteromedial papillary muscle (PPM) (4/19); type 2 FTs ran between the septum and the PPM apex (3/19), while in type 3, the connection occurred between the septum and apex (11/19) or between the septum and the LV free wall (1/19). The effective ILVT ablation sites were situated at the FT-PPM (3/19) and the FT-septum (16/19) attachment sites. CONCLUSIONS: This series demonstrates the association between Purkinje fibers and FTs during catheter ablation of ILVT and verifies that left ventricular FTs are an important substrate in this type of tachycardia.

Prognostic value of heart rate variability in atrial fibrillation recurrence following catheter ablation: A systematic review and meta-analysis.

Background: Atrial fibrillation (AF) has been a worldwide health issue with increasing prevalence and mortality. Recently, increasing attention has been gained to the relationship between heart rate variability (HRV) and the clinical prognosis of AF catheter ablation. We aimed to evaluate the prognostic value of HRV in AF recurrence. Methods: We systematically searched Web of Science, PubMed, and Embase from inception until 17 August 2022 to conduct the systematic review and meta-analysis. We included the studies reporting the predictive value of HRV parameters for AF recurrence or in which HRV parameters in AF recurrence and non-recurrence groups were individually reported. Results: Finally, we enrolled 16 studies, including 2,352 patients. Higher rMSSD could independently predict AF recurrence following catheter ablation (OR: 1.02, 95% CI: 1.00-1.04; p = 0.03). Higher HF (OR: 1.55, 95% CI: 1.05-2.28; p = 0.03) and lower LF/HF (OR: 1.12, 95% CI: 1.03-1.20; p = 0.004) could independently predict AF recurrence within 1 year. Higher SDNN (OR: 1.02, 95% CI: 101-1.02; p = 0.0006) could independently predict AF recurrence among patients with paroxysmal AF. Almost all HRV parameters within 3 days after catheter ablation and lnHF, lnLF, and rMSSD at 3 months after catheter ablation performed significant differences in AF recurrence and non-recurrence groups. Conclusion: Heart rate variability, especially higher rMSSD (within short-term and long-term periods), was closely related to recurrent AF following catheter ablation, highlighting the clinical importance of HRV in the prognosis of AF following catheter ablation.

Inflammatory Indicators and Hematological Indices in Contrast-Induced Nephropathy Among Patients Receiving Coronary Intervention: A Systematic Review and Meta-Analysis.

Strong inflammatory indicators such as C-reactive protein (CRP), high-sensitivity CRP (hsCRP), and hematological indices, including platelet to lymphocyte ratio (PLR), neutrophil to lymphocyte ratio (NLR), hematocrit (HCT), and red blood cell distribution width (RDW), may be related with contrast-induced nephropathy (CIN). Our meta-analysis aimed at exploring the relationship between these indicators and CIN incidence among patients undergoing coronary intervention. Clinical studies were retrieved from the electronic databases of PubMed, EMBASE, Google Scholar, Clinical Trials, and Science Direct from their inception to June 3, 2020. Meta-analysis was performed on pooled eligible studies. Finally, 26 studies involving 29 454 patients were included. Pooled analysis revealed that patients with higher CRP (odds ratio [OR] = 1.06, 95% CI: 1.01-1.12, P = .02), hsCRP (OR = 1.03, 95% CI: 1.01-1.06, P = .004), NLR (OR = 1.11, 95% CI: 1.01-1.20, P = .02), RDW (OR = 1.35, 95% CI: 1.19-1.53, P < .001), and lower HCT (OR = 0.94, 95% CI: 0.92-0.97, P = .003) all exhibited significantly higher CIN rates, but there was no significant association between PLR and CIN risk (OR = 1.12, 95% CI: 0.99-1.26, P = .07). Pre-angiography CRP/hsCRP and some hematological indices are associated with CIN.

Intracoronary pressure gradient measurement in acute myocardial infarction patients with the no-reflow phenomenon during primary percutaneous coronary intervention.

BACKGROUND: Various experimental and clinical studies have reported on coronary microcirculatory dysfunction ("no-reflow" phenomenon). Nevertheless, pathogenesis and effective treatment are yet to be fully elucidated. This study aimed to measure the intracoronary pressure gradient in the no-reflow artery during emergent percutaneous coronary intervention and explore the potential mechanism of no-reflow. METHODS: From September 1st, 2018 to June 30th, 2019, intracoronary pressure in acute myocardial infarction patient was continuously measured by aspiration catheter from distal to proximal segment in the Department of Coronary Care Unit, Tianjin Chest Hospital, respectively in no-reflow arteries (no-reflow group) and arteries with thrombolysis in myocardial infarction-3 flow (control group). At least 12 cardiac cycles were consecutively recorded when the catheter was pulled back. The forward systolic pressure gradient was calculated as proximal systolic pressure minus distal systolic pressure. Comparison between groups was made using the Student t test, Mann-Whitney U-test or Chi-square test, as appropriate. RESULTS: Intracoronary pressure in 33 no-reflow group and 26 in control group were measured. The intracoronary forward systolic pressure gradient was -1.3 (-4.8, 0.7) and 3.8 (0.8, 8.8) mmHg in no-reflow group and control group (Z = -3.989, P < 0.001), respectively, while the forward diastolic pressure gradient was -1.0 (-3.2, 0) and 4.6 (0, 16.5) mmHg in respective groups (Z = -3.851, P < 0.001). Moreover, the intracoronary forward pressure gradient showed significant difference between that before and after nicorandil medication (Z = -3.668, P < 0.001 in systolic pressure gradient and Z = -3.530, P < 0.001 in diastolic pressure gradient). CONCLUSIONS: No reflow during emergent coronary revascularization is significantly associated with local hemodynamic abnormalities in the coronary arteries. Intracoronary nicorandil administration at the distal segment of a coronary artery with an aspiration catheter could improve the microcirculatory dysfunction and resume normal coronary pressure gradient. CLINICAL TRIAL REGISTRATION: www.ClinicalTrials.gov (No. NCT03600259).

Inflammatory and Hematological Indices as Simple, Practical Severity Predictors of Microdysfunction Following Coronary Intervention: A Systematic Review and Meta-Analysis.

C-reactive protein (CRP) and high-sensitivity CRP (hsCRP), along with a series of hematological indices, platelet to lymphocyte ratio (PLR), neutrophil to lymphocyte ratio (NLR), mean platelet volume (MPV), platelet distribution width (PDW), and red blood cell distribution width (RDW), are regarded to be related to the incidence of no-reflow or slow flow. Clinical studies were retrieved from the electronic databases of PubMed, EMBASE, Google Scholar, Clinical Trials, and science direct from their inception to August 24, 2019. A total of 21 studies involving 7403 patients were included in the meta-analysis. Pooled analysis results revealed patients with higher hsCRP (odds ratio [OR] = 1.03, 95% confidence interval [CI], 1.01-1.05, P = .006), hsCRP (OR = 1.04, 95% CI: 1.0-1.08, P = .012), NLR (OR = 1.23, 95% CI: 1.11-1.37, P < .0001), PLR (OR = 1.13, 95% CI: 1.07-1.20, P < .0001), and MPV (OR = 2.13, 95% CI: 1.57-2.90, P < .0001) all exhibited significantly higher no-reflow incidence, but there was no significant association between no-reflow risk and RDW or PDW. Patients with higher CRP/hsCRP also performed higher rate of slow flow (OR = 1.06, 95% CI: 1.01-1.11, P = .018). Preangiographic CRP/hsCRP could independently predict no-reflow and slow flow. Moreover, some hematological indices are associated with no-flow.

Predictive Value of Hepatorenal Status in Contrast-Induced Nephropathy Among Patients Receiving Coronary Angiography and/or Intervention: A Systematic Review and Meta-Analysis.

BACKGROUND: Low serum albumin, high blood urea nitrogen (BUN), and uric acid are regarded closely related to the incidence of contrast-induced nephropathy (CIN), whereas it remains unclear whether they can function as predictors of CIN onset. The objective of this systematic review and meta-analysis was to explore the association between abovementioned indicators and CIN incidence rate in patients receiving coronary angiography (CAG) and/or intervention. METHODS: Clinical studies were retrieved from the electronic databases of PubMed, EMBASE, Google Scholar, Clinical Trials, and ScienceDirect from their inception to July 13, 2018. Meta-analysis was performed on pooled eligible studies to determine whether these hepatorenal indicators were associated with CIN. RESULTS: A total of 18 studies involving 16 171 patients were included in the meta-analysis. Pooled analysis results revealed that patients with hypoalbuminemia (odds ratio [OR] = 3.09, 95% confidence interval [CI] = 1.44-6.64, P = .004) and hyperuricemia (OR = 1.32, 95% CI = 1.15-1.50, P < .0001) both exhibited significantly higher CIN rates, regardless of the study design, renal function, and whether urgent clinical situation or not. However, there was no significant association between serum BUN and CIN risk. CONCLUSION: Hypoalbuminemia and hyperuricemia are independently associated with the occurrence of CIN among the patients undergoing CAG and/or intervention.

High Serum sTREM-1 Correlates With Myocardial Dysfunction and Predicts Prognosis in Septic Patients.

OBJECTIVE: This study aimed to evaluate the predictive and prognostic value of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) in patients with myocardial dysfunction induced by severe sepsis and septic shock. MATERIALS AND METHODS: A total of 84 patients with severe sepsis and septic shock were enrolled between May 2013 and December 2014.The patients were monitored by pulse indicator continuous cardiac output system and divided into myocardial depression group (cardiac function index [CFI] < 4.1/minute, n = 37) and nonmyocardial depression group (CFI ≥ 4.1/minute, n = 47 ). Additionally, the patients were divided into survival group (n = 40) and nonsurvival group (n = 44) based on 28-day mortality. Hemodynamic parameters and serum sTREM-1, B-type natriuretic peptide (BNP) and cardiac troponin I (cTnI) levels were collected on days 1, 3 and 5 after admission to intensive care unit. RESULTS: (1) The serum values of sTREM-1, BNP and cTnI in myocardial depression group were higher than those in nonmyocardial depression group (P < 0.01); and CFI, cardiac index, stroke volume, global ejection fraction and left ventricular contractility index (dpmax) in myocardial depression group were lower than those in nonmyocardial depression group on day 1 (P < 0.05); (2) serum sTREM-1 negatively correlated with left ventricular ejection fraction, CFI, cardiac index, global ejection fraction and dpmax, and it positively correlated with BNP and cTnI (P < 0.01); (3) the area under the receiver operating characteristics curve for sTREM-1 in the prediction of myocardial depression was 0.671 with a sensitivity of 83.8% and a specificity of 46.8% when cutoff point was 174.5ng/mL, the power of predicting septic depression for sTREM-1 was lower than that of BNP; logistic regression analysis showed that serum sTREM-1 was not an independent predictor of septic myocardial depression; the area under the receiver operating characteristics curve was 0.773 for sTREM-1 in predicting outcome with a sensitivity of 86.4% and a specificity of 80% when cutoff point was 182.3ng/mL, the power of predicting prognosis for sTREM-1 was superior to those of BNP and cTnI; (4) there was a decrease trend for sTREM-1 levels and an increasing trend for CFI in the survival group (P < 0.05). CONCLUSIONS: Myocardial dysfunction is common in patients with severe sepsis and septic shock and high serum levels of sTREM-1 correlates with myocardial dysfunction to some extent but is not an independent predictor, which more importantly showed prognostic value for septic shock outcome.

High uric acid level predicts left atrial thrombus or spontaneous echo contrast detected by transesophageal echocardiography: Meta-analysis and systematic review.

BACKGROUND: Recent observational studies have suggested that the patients with hyperuricemia have a higher risk of having left atrial thrombus (LATH) or left atrial spontaneous echo contrast (LASEC) by transesophageal echocardiography (TEE), while the ultimate predictive value of a high uric acid (UA) level on LATH/LASEC remained obscure. METHODS: We searched the PubMed and Cochrane clinical trials databases up to July 2015. Following screening the 369 initially identified studies, we analyzed six observational studies with 2381 patients. RESULTS: The meta-analysis of these studies showed that an elevated serum UA level was associated with a higher likelihood of LATH/LASEC (OR = 1.59, 95%CI 1.13-2.23, P = 0.008), while significant differences exist among individual trials (P < 0.00001 and I2 = 85%). Sensitivity analysis failed to find any heterogeneity. CONCLUSION: An elevated UA level was associated with a higher risk of detecting a left atrial abnormality represented by LATH/LASEC.

High Killips Class as a Predictor of New-onset Atrial Fibrillation Following Acute Myocardial Infarction: Systematic Review and Meta-analysis.

BACKGROUND: Recent observational studies have shown that patients with higher Killips score (>I) have higher risk of new-onset atrial fibrillation (NOAF) following acute myocardial infarction (AMI), while others drew a neutral conclusion. The ultimate predictive value of high Killips class on NOAF remained obscure. METHODS: PubMed, Web of Science, China National Knowledge Infrastructure, and the Cochrane Controlled Trials Register Databases were searched until February 2015. Of the 3732 initially identified studies, 5 observational studies with 10,053 patients were analyzed. RESULTS: The meta-analysis of these studies showed that higher Killips score on admission was associated with higher incidence of NOAF following AMI (odds ratio = 2.29, 95% confidence interval 1.96-2.67, P < 0.00001), while no significant differences exist among individual trials (P = 0.14 and I2 = 43%). CONCLUSIONS: Killips class >I was associated with the higher opportunity of developing NOAF following AMI.

Anemia and Inflammation in ST-Segment Elevation Myocardial Infarction.

BACKGROUND: To investigate the factors predicting the onset of major adverse cardiovascular events (MACEs) after primary percutaneous coronary intervention for ST-segment elevation myocardial infarction (STEMI) patients. METHODS: Two hundred forty-eight STEMI patients (61.4 ± 10.8 years, 186 men) who underwent successful primary percutaneous coronary intervention were enrolled. Patients were followed-up for 1 year. Univariate, multivariate analyses, and receiver operating characteristic curve analysis were performed to determine the factors predicting MACEs. RESULTS: There were 36 patients (14.5%) who experienced MACEs in the follow-up period. Multivariate logistic regression analysis demonstrated that hemoglobin (HgB) (odds ratio = 0.972; 95% CI, 0.948-0.998; P = 0.033), neutrophil/lymphocyte ratio (NLR) (odds ratio = 1.511; 95% CI, 1.148-1.987; P = 0.003), Global Registry of Acute Coronary Event score, and postprocedure left ventricular ejection fraction (LVEF) were independent predictors of MACEs. Further subgroup analysis showed higher NLR (> 8.61), Global Registry of Acute Coronary Event score (> 167) and lower HgB (< 131 g/L) all show superior predictive value for patients with relatively higher LVEF (> 48%); moreover, the c-statistic of NLR and HgB both exceed 0.7. However, among patients with lower LVEF (≤ 48%), higher NLR and lower HgB lost the ability for predicting 1 year MACEs independently. In addition, abnormally higher NLR (> 8) could predict 1-month MACEs efficiently. CONCLUSIONS: In summary, among STEMI patients, elevated NLR, decreased HgB level on admission both predicted 1-year MACEs independently, especially for those with relatively preserved LVEF (> 48%). Besides, abnormally higher NLR on admission should attract their attention for short-term MACEs.