Search

Chemokines are from a family of secreted cytokines that direct the trafficking of immune cells to coordinate immune responses. Chemokines are involved in numerous disease states, including responding to infections, autoimmune disorders, and cancer metastasis. Ther are chemokines, like CCL21, that signal for cellular migration through the activation of G protein-coupled receptors, like CCR7, through interaction with the receptor's extracellular N-terminus, loops, and core of the receptor. CCL21 is involved in routine immune surveillance but can also attract metastasizing cancer cells to lymph nodes. P-selectin glycoprotein ligand 1 (PSGL1) has a role in cellular adhesion during chemotaxis and is a transmembrane signaling molecule. PSGL1 expression enhances chemotactic responses of T cells to CCL21. Here NMR studies indicate the binding sites on CCL21 for the N-termini or PSGL1 and CCR7 overlap, and binding of the N-termini of PSGL1 and CCR7 is competitive.

Background: Incretins are a group of glucose-lowering drugs with favourable cardiovascular (CV) effects against neoatherosclerosis. Incretins' potential effect in stent failure is unknown. The aim of this study is to determine if incretin treatment decreases the risk of stent-thrombosis (ST), and/or in-stent restenosis (ISR) after percutaneous coronary intervention (PCI) with implanted drug-eluting stents (DES)., Methods: Observational study including all diabetes patients who underwent PCI with DES in Sweden from 2007 to 2017. By merging 5 national registers, the information on patient characteristics, outcomes and drug dispenses was retrieved. Cox regression analysis with estimated hazard ratios (HRs) adjusted for confounders with 95% confidence intervals (CIs) was used to analyse for the occurrence of ST/ISR, and major adverse cardiovascular events (MACE). A subgroup analysis for the type of incretin treatment was performed., Results: In total 18,505 diabetes patients (30% women) underwent PCI, and 32,463 DES were implanted. Of those, 10% (3449 DES in 1943 patients) were treated with incretins. Median follow-up time was 995 days (Control Group) vs. 771 days (Incretin Group). No significant difference in the risk of ST/ISR was found neither for the main study group (HR:0.98 95% CI:0.80-1.19) nor for the subgroups. No reduction of the risk of MACE (HR:0.96 95% CI:0.88-1.06) was observed. There was a 26% lower risk for CV death in favour of incretin treated patients (HR:0.74 95% CI:0.57-0.95)., Conclusion: In diabetes patients who underwent PCI incretin treatment was not associated with lower risk of stent failure, but with lower risk of CV death., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objective: To evaluate the long-term efficacy of three currently available drug coated balloons (DCB) for the treatment of de-novo coronary lesions., Methods: This was a retrospective analysis of prospectively collected data from the Swedish Coronary Angiography and Angioplasty Registry. Between 2009 and 2017, three currently available DCB brands used in the treatment of de novo lesions were included. Outcomes were clinically driven restenosis and target lesion thrombosis (TLT) (per device) and major adverse cardiac events (MACE) including death, myocardial infarction or target vessel revascularization (per patient) at 4 years. Multivariable Cox regression models were used to adjust for differences., Results: We included 6715 lesions treated with DCBs, 4483 SeQuent® Please (S-DCB), 1071 IN.PACT Falcon (I-DCB) and 1161 Pantera® Lux (P-DCB), in 5670 patients. The mean DCB diameter was 2.4 mm. Bailout stenting occurred in 6.7% of lesions. Angiographic success was 98.5%. The overall cumulative rate of restenosis was 5.5% (299 events). The risk for reported restenosis did not significantly differ between I-DCB vs S-DCB, adjusted hazard ratio (aHR) 0.96; 95% confidence interval (CI) 0.69-1.34, P-DCB vs S-DCB aHR 0.88; 95% CI 0.63-1.23 and I-DCB vs P-DCB aHR 1.10; 95% CI 0.72-1.68. The cumulative risk for TLT was 0.8% in all three DCBs. The risk for MACE or individual components of MACE did not differ between the three patient-groups., Conclusion: In de novo coronary lesions, we found comparable long-term efficacy with three currently available DCB brands. DCB angioplasty was feasible with low risk for long-term restenosis and TLT., Competing Interests: Declaration of Competing Interest D. Venetsanos, E. Omerovic, F. Böhm, G, Sarno, C. Pagonis, N. Witt, F. Calais, J. Jurga, S. Völz, S. Koul, G. Olivercrona, S. James and J. Alfredsson have nothing to declare., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Coronary microvascular dysfunction (CMVD) is associated with adverse cardiovascular outcome. We aimed to determine the prevalence of CMVD and factors related to index of microcirculatory resistance (IMR) in consecutive patients with chronic coronary syndrome (CCS) undergoing elective coronary angiography., Methods and Results: Non-interventional physicians enrolled 274 patients with CCS before angiography, to minimize selection bias by PCI-operators. Fractional flow reserve (FFR) and IMR were measured in the LAD. Subjects with extensively diseased LAD, no measures due to technical reasons or violation of protocol were excluded from the analysis (n = 54). The proportion of patients with IMR corrected for collateral flow (IMR corr ) >25 units was 25% (95% confidence interval [CI] 19%-31%) in all 220 patients. In subjects with FFR ≤0.80 in the LAD the proportion of IMR corr  > 25 units was 21% (95% CI 13%-30%) as compared to subjects with FFR >0.80, 29% (95% CI 21%-36%), p = .268. Haemoglobin (p < .005; r2 = 0.084), FFR in the LAD (p = .001; r2 = 0.049), creatinine clearance (p = .001; r 2  = 0.049; inversely), and NT-proBNP (p = .038; r 2  = 0.021) were independently associated with IMR corr in multivariate linear regression analysis., Conclusions: We report that IMR corr is associated with renal dysfunction, NT-proBNP, FFR in the LAD and, for the first time, blood haemoglobin. One in four of patients referred for coronary angiography due to CCS have CMVD defined as IMR corr  > 25 in the LAD., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objectives: The aim of this study was to investigate the outcomes of patients with de novo lesions in small coronary vessels undergoing percutaneous coronary intervention (PCI) with drug-coated balloons (DCBs) or newer-generation drug-eluting stents (n-DES)., Background: Notwithstanding the available evidence from a few randomized clinical trials and meta-analyses, the best device for PCI in patients with small-vessel coronary artery disease is not yet established., Methods: The study included all consecutive patients with de novo lesions in small coronary vessels undergoing PCI in Sweden from April 2009 to July 2017. A small coronary vessel was defined by a device diameter ≤2.5 mm. The primary outcomes were restenosis and definite target lesion thrombosis at 3-year follow-up. The secondary outcomes were the occurrence of all-cause death and myocardial infarction., Results: The study population included 14,788 patients: 1,154 treated with DCBs and 13,634 with n-DES. Overall, 35,541 PCIs were performed using 2,503 DCBs and 33,038 n-DES. The propensity score-adjusted regression analysis showed a significantly higher risk for restenosis in the DCB group compared with the n-DES group (adjusted hazard ratio [HR]: 2.027; 95% confidence interval [CI]: 1.537 to 2.674). Conversely, no difference in the risk for target lesion thrombosis (adjusted HR: 0.741; 95% CI: 0.412 to 1.331) was detected. The risk for all-cause death (adjusted HR: 1.178; 95% CI: 0.992 to 1.399) and myocardial infarction (adjusted HR: 1.251; 95% CI: 0.960 to 1.629) was comparable between groups., Conclusions: Because of the significantly higher risk for restenosis up to 3 years, this research suggests that DCBs are not an equally effective alternative to n-DES for percutaneous treatment of small coronary vessels., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: In this substudy of the DETO2X-AMI (An Efficacy and Outcome Study of Supplemental Oxygen Treatment in Patients With Suspected Myocardial Infarction) trial, the authors aimed to assess the analgesic effect of moderate-flow oxygen supplementation in patients with suspected acute myocardial infarction (AMI) treated with percutaneous coronary intervention (PCI) and to study the effect of oxygen supplementation on the use of opiates and sedatives during PCI., Background: Routine oxygen in normoxemic patients with AMI does not provide clinical benefit. However, oxygen may relieve ischemic pain., Methods: Patients were randomly allocated to oxygen or ambient air according to the main study protocol. After PCI, peak level of pain during PCI was measured by the Visual Analogue Scale. The total amount of opiates and sedatives was reported., Results: A total of 622 patients were enrolled: 330 in the oxygen group and 292 in the ambient air group. There was no significant difference in peak level of pain (oxygen 4.0 [1.0 to 6.0] vs. air 3.0 [0.6 to 6.0]; p = 0.37), use of opiates (mg) (oxygen 0.0 [0.0 to 3.0] vs. air 0.0 [0.0 to 3.0]; p = 0.31), or use of sedatives between the groups (median [interquartile range]) (oxygen 2.5 [0.0 to 2.5] vs. air 2.5 [0.0 to 2.5]; p = 0.74)., Conclusions: In the present study, the authors did not find any analgesic effect of routine oxygen as compared with ambient air, and no differences in the use of sedatives and opiates during PCI. Our results indicate that moderate-flow oxygen supplementation does not relieve pain in normoxemic patients with suspected AMI undergoing treatment with PCI and should thus not be used for this purpose., (Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: The goal of this study was to investigate sex differences in adenosine-free coronary pressure indexes., Background: Several adenosine-free coronary pressure wire indexes have been proposed to assess the functional significance of coronary artery lesions; however, there is a theoretical concern that sex differences may affect diagnostic performance because of differences in resting flow and distal myocardial mass., Methods: In this CONTRAST (Can Contrast Injection Better Approximate FFR Compared to Pure Resting Physiology?) substudy, contrast fractional flow reserve (cFFR), obtained during contrast-induced submaximal hyperemia, the instantaneous wave-free ratio (iFR), and distal/proximal coronary pressure ratio (Pd/Pa) were compared with fractional flow reserve (FFR) in 547 men and 216 women. Using FFR ≤0.8 as a reference, the diagnostic performance of each index was compared., Results: Men and women had similar diameter stenosis (p = 0.78), but women were less likely to have FFR ≤0.80 than men (42.5% vs. 51.5%, p = 0.04). Sensitivity was similar among cFFR, iFR, and Pd/Pa when comparing women and men, respectively (cFFR, 77.5% vs. 75.3%; p = 0.69; iFR, 84.9% vs. 79.4%; p = 0.30; Pd/Pa, 78.8% vs. 77.3%; p = 0.78). cFFR was more specific than iFR or Pd/Pa regardless of sex (cFFR, 94.3% vs. 95.8%; p = 0.56; iFR, 75.6% vs. 80.1%; p = 0.38; Pd/Pa, 80.6% vs. 78.7%; p = 0.69). By receiver-operating characteristic curve analysis, cFFR provided better diagnostic accuracy than resting indexes irrespective of sex (p ≤ 0.0001)., Conclusions: Despite the theoretical concern, the diagnostic sensitivity and specificity of cFFR, iFR, and Pd/Pa did not differ between the sexes. Irrespective of sex, cFFR provides the best diagnostic performance., (Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: This study compared the diagnostic performance with adenosine-derived fractional flow reserve (FFR) ≤0.8 of contrast-based FFR (cFFR), resting distal pressure (Pd)/aortic pressure (Pa), and the instantaneous wave-free ratio (iFR)., Background: FFR objectively identifies lesions that benefit from medical therapy versus revascularization. However, FFR requires maximal vasodilation, usually achieved with adenosine. Radiographic contrast injection causes submaximal coronary hyperemia. Therefore, intracoronary contrast could provide an easy and inexpensive tool for predicting FFR., Methods: We recruited patients undergoing routine FFR assessment and made paired, repeated measurements of all physiology metrics (Pd/Pa, iFR, cFFR, and FFR). Contrast medium and dose were per local practice, as was the dose of intracoronary adenosine. Operators were encouraged to perform both intracoronary and intravenous adenosine assessments and a final drift check to assess wire calibration. A central core lab analyzed blinded pressure tracings in a standardized fashion., Results: A total of 763 subjects were enrolled from 12 international centers. Contrast volume was 8 ± 2 ml per measurement, and 8 different contrast media were used. Repeated measurements of each metric showed a bias <0.005, but a lower SD (less variability) for cFFR than resting indexes. Although Pd/Pa and iFR demonstrated equivalent performance against FFR ≤0.8 (78.5% vs. 79.9% accuracy; p = 0.78; area under the receiver-operating characteristic curve: 0.875 vs. 0.881; p = 0.35), cFFR improved both metrics (85.8% accuracy and 0.930 area; p < 0.001 for each) with an optimal binary threshold of 0.83. A hybrid decision-making strategy using cFFR required adenosine less often than when based on either Pd/Pa or iFR., Conclusions: cFFR provides diagnostic performance superior to that of Pd/Pa or iFR for predicting FFR. For clinical scenarios or health care systems in which adenosine is contraindicated or prohibitively expensive, cFFR offers a universal technique to simplify invasive coronary physiological assessments. Yet FFR remains the reference standard for diagnostic certainty as even cFFR reached only ∼85% agreement., (Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)