| 1. |
- Bryl-Górecka, Paulina, et al.
(författare)
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Bilberry Supplementation after Myocardial Infarction Decreases Microvesicles in Blood and Affects Endothelial Vesiculation
- 2020
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Ingår i: Molecular Nutrition & Food Research. - : Wiley-VCH Verlagsgesellschaft. - 1613-4125 .- 1613-4133. ; 64:20
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Tidskriftsartikel (refereegranskat)abstract
- Scope: Diet rich in bilberries is considered cardioprotective, but the mechanisms of action are poorly understood. Cardiovascular disease is characterized by increased proatherogenic status and high levels of circulating microvesicles (MVs). In an open-label study patients with myocardial infarction receive an 8 week dietary supplementation with bilberry extract (BE). The effect of BE on patient MV levels and its influence on endothelial vesiculation in vitro is investigated.Methods and results: MVs are captured with acoustic trapping and platelet-derived MVs (PMVs), as well as endothelial-derived MVs (EMVs) are quantified with flow cytometry. The in vitro effect of BE on endothelial extracellular vesicle (EV) release is examined using endothelial cells and calcein staining. The mechanisms of BE influence on vesiculation pathways are studied by Western blot and qRT-PCR. Supplementation with BE decreased both PMVs and EMVs. Furthermore, BE reduced endothelial EV release, Akt phosphorylation, and vesiculation-related gene transcription. It also protects the cells from P2X(7)-induced EV release and increase in vesiculation-related gene expression.Conclusion: BE supplementation improves the MV profile in patient blood and reduces endothelial vesiculation through several molecular mechanisms related to the P2X(7)receptor. The findings provide new insight into the cardioprotective effects of bilberries.
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| 2. |
- Ebner, Florian, et al.
(författare)
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Serum GFAP and UCH-L1 for the prediction of neurological outcome in comatose cardiac arrest patients
- 2020
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Ingår i: Resuscitation. - : Elsevier BV. - 0300-9572. ; 154, s. 61-68
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Neurological outcome prediction is crucial early after cardiac arrest. Serum biomarkers released from brain cells after hypoxic-ischaemic injury may aid in outcome prediction. The only serum biomarker presently recommended in the European Resuscitation Council prognostication guidelines is neuron-specific enolase (NSE), but NSE has limitations. In this study, we therefore analyzed the outcome predictive accuracy of the serum biomarkers glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal hydrolase-L1 (UCH-L1) in patients after cardiac arrest. Methods: Serum GFAP and UCH-L1 were collected at 24, 48 and 72 h after cardiac arrest. The primary outcome was neurological function at 6-month follow-up assessed by the cerebral performance category scale (CPC), dichotomized into good (CPC1-2) and poor (CPC3-5). Prognostic accuracies were tested with receiver-operating characteristics by calculating the area under the receiver-operating curve (AUROC) and compared to the AUROC of NSE. Results: 717 patients were included in the study. GFAP and UCH-L1 discriminated between good and poor neurological outcome at all time-points when used alone (AUROC GFAP 0.88–0.89; UCH-L1 0.85–0.87) or in combination (AUROC 0.90–0.91). The combined model was superior to GFAP and UCH-L1 separately and NSE (AUROC 0.75–0.85) at all time-points. At specificities ≥95%, the combined model predicted poor outcome with a higher sensitivity than NSE at 24 h and with similar sensitivities at 48 and 72 h. Conclusion: GFAP and UCH-L1 predicted poor neurological outcome with high accuracy. Their combination may be of special interest for early prognostication after cardiac arrest where it performed significantly better than the currently recommended biomarker NSE.
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| 3. |
- Akil, Shahnaz, et al.
(författare)
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Qualitative assessments of myocardial ischemia by cardiac MRI and coronary stenosis by invasive coronary angiography in relation to quantitative perfusion by positron emission tomography in patients with known or suspected stable coronary artery disease
- 2020
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Ingår i: Journal of Nuclear Cardiology. - : Springer Science and Business Media LLC. - 1071-3581 .- 1532-6551. ; 27:6, s. 2351-2359
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Tidskriftsartikel (refereegranskat)abstract
- Background: To relate findings of qualitative evaluation of first-pass perfusion-CMR and anatomical evaluation on coronary angiography (CA) to the reference standard of quantitative perfusion, cardiac PET, in patients with suspected or known stable coronary artery disease (CAD). Methods and Results: Forty-one patients referred for CA due to suspected stable CAD, prospectively performed adenosine stress/rest first-pass perfusion-CMR as well as 13N-NH3 PET on the same day, 4 ± 3 weeks before CA. Angiographers were blinded to PET and CMR results. Regional myocardial flow reserve (MFR) < 2.0 on PET was considered pathological. Vessel territories with stress-induced ischemia by CMR or vessels with stenosis needing revascularization had a significantly lower MFR compared to those with no regional stress-induced ischemia or vessels not needing revascularization (P < 0.001). In 4 of 123 vessel territories with stress-induced ischemia by CMR, PET showed a normal MFR. In addition, 12 of 123 vessels that underwent intervention showed normal MFR assessed by PET. Conclusion: The limited performance of qualitative assessment of presence of stable CAD with CMR and CA, when related to quantitative 13N-NH3 cardiac PET, shows the need for fully quantitative assessment of myocardial perfusion and the use of invasive flow reserve measurements for CA, to confirm the need of elective revascularization.
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| 4. |
- Jakobsen, Janus Christian, et al.
(författare)
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Targeted hypothermia versus targeted normothermia after out-of-hospital cardiac arrest: a statistical analysis plan.
- 2020
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Ingår i: Trials. - : Springer Science and Business Media LLC. - 1745-6215. ; 21:1
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Tidskriftsartikel (refereegranskat)abstract
- To date, targeted temperature management (TTM) is the only neuroprotective intervention after resuscitation from cardiac arrest that is recommended by guidelines. The evidence on the effects of TTM is unclear.The Targeted Hypothermia Versus Targeted Normothermia After Out-of-hospital Cardiac Arrest (TTM2) trial is an international, multicentre, parallel group, investigator-initiated, randomised, superiority trial in which TTM with a target temperature of 33 °C after cardiac arrest will be compared with a strategy to maintain normothermia and active treatment of fever (≥ 37.8 °C). Prognosticators, outcome assessors, the steering group, the trial coordinating team, and trial statisticians will be blinded to treatment allocation. The primary outcome will be all-cause mortality at 180 days after randomisation. We estimate a 55% mortality in the targeted normothermia group. To detect an absolute risk reduction of 7.5% with an alpha of 0.05 and 90% power, 1900 participants will be enrolled. The secondary neurological outcome will be poor functional outcome (modified Rankin scale 4-6) at 180 days after cardiac arrest. In this paper, a detailed statistical analysis plan is presented, including a comprehensive description of the statistical analyses, handling of missing data, and assessments of underlying statistical assumptions. Final analyses will be conducted independently by two qualified statisticians following the present plan.This SAP, which was prepared before completion of enrolment, should increase the validity of the TTM trial by mitigation of analysis-bias.
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| 5. |
- Andell, Pontus, et al.
(författare)
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Oxygen therapy in suspected acute myocardial infarction and concurrent normoxemic chronic obstructive pulmonary disease : a prespecified subgroup analysis from the DETO2X-AMI trial.
- 2020
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Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 2048-8726 .- 2048-8734. ; 9:8, s. 984-992
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The DETermination of the role of Oxygen in suspected Acute Myocardial Infarction (DETO2X-AMI) trial did not find any benefit of oxygen therapy compared to ambient air in normoxemic patients with suspected acute myocardial infarction. Patients with chronic obstructive pulmonary disease may both benefit and be harmed by supplemental oxygen. Thus we evaluated the effect of routine oxygen therapy compared to ambient air in normoxemic chronic obstructive pulmonary disease patients with suspected acute myocardial infarction.METHODS AND RESULTS: =0.77]); there were no significant treatment-by-chronic obstructive pulmonary disease interactions.CONCLUSIONS: Although chronic obstructive pulmonary disease patients had twice the mortality rate compared to non-chronic obstructive pulmonary disease patients, this prespecified subgroup analysis from the DETO2X-AMI trial on oxygen therapy versus ambient air in normoxemic chronic obstructive pulmonary disease patients with suspected acute myocardial infarction revealed no evidence for benefit of routine oxygen therapy consistent with the main trial's findings.CLINICAL TRIALS REGISTRATION: NCT02290080.
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| 6. |
- Attar, Rubina, et al.
(författare)
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Higher risk of major adverse cardiac events after acute myocardial infarction in patients with schizophrenia
- 2020
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Ingår i: Open Heart. - : BMJ. - 2053-3624. ; 7:2
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Patients with schizophrenia are a high-risk population due to higher prevalences of cardiovascular risk factors and comorbidities that contribute to shorter life expectancy.PURPOSE: To investigate patients with and without schizophrenia experiencing an acute myocardial infarction (AMI) in relation to guideline recommended in-hospital management, discharge medications and 5-year major adverse cardiac events (MACE: composite of all-cause mortality, rehospitalisation for reinfarction, stroke or heart failure).METHODS: All patients with schizophrenia who experienced AMI during 2000-2018 were identified (n=1008) from the nationwide Swedish Web-system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies registry and compared with AMI patients without schizophrenia (n=2 85 325). Kaplan-Meier survival curves and multivariable Cox regression models were used to compare the populations.RESULTS: Patients with schizophrenia presented with AMI approximately 10 years earlier (median age 64 vs 73 years), and had higher prevalences of diabetes, heart failure and chronic obstructive pulmonary disease. They were less likely to be invasively investigated or discharged with aspirin, P2Y12 inhibitors, ACE inhibitors/angiotensin II receptor blockers, beta-blockers and statins (all p<0.005). AMI patients with schizophrenia had higher adjusted risk of MACE (aHR=2.05, 95% CI 1.63 to 2.58), mortality (aHR=2.38, 95% CI 1.84 to 3.09) and hospitalisation for heart failure (aHR=1.39, 95% CI 1.04 to 1.86) compared with AMI patients without schizophrenia.CONCLUSION: Patients with schizophrenia experienced an AMI almost 10 years earlier than patients without schizophrenia. They less often underwent invasive procedures and were less likely to be treated with guideline recommended medications at discharge, and had more than doubled risk of MACE and all-cause mortality. Improved primary and secondary preventive measures, including adherence to guideline recommendations, are warranted and may improve outcome.
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| 7. |
- Bikdeli, Behnood, et al.
(författare)
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Individual Patient Data Pooled Analysis of Randomized Trials of Bivalirudin versus Heparin in Acute Myocardial Infarction : Rationale and Methodology
- 2020
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Ingår i: Thrombosis and Haemostasis. - : Georg Thieme Verlag KG. - 0340-6245 .- 2567-689X. ; 120:2, s. 348-361
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Tidskriftsartikel (refereegranskat)abstract
- Background Individual randomized controlled trials (RCTs) of periprocedural anticoagulation with bivalirudin versus heparin during percutaneous coronary intervention (PCI) have reported conflicting results. Study-level meta-analyses lack granularity to adjust for confounders, explore heterogeneity, or identify subgroups that may particularly benefit or be harmed.Objective To overcome these limitations, we sought to develop an individual patient-data pooled database of RCTs comparing bivalirudin versus heparin.Methods We conducted a systematic review to identify RCTs in which ≥1,000 patients with acute myocardial infarction (AMI) undergoing PCI were randomized to bivalirudin versus heparin.Results From 738 identified studies, 8 RCTs met the prespecified criteria. The principal investigators of each study agreed to provide patient-level data. The data were pooled and checked for accuracy against trial publications, with discrepancies addressed by consulting with the trialists. Consensus-based definitions were created to resolve differing antithrombotic, procedural, and outcome definitions. The project required 3.5 years to complete, and the final database includes 27,409 patients (13,346 randomized to bivalirudin and 14,063 randomized to heparin).Conclusion We have created a large individual patient database of bivalirudin versus heparin RCTs in patients with AMI undergoing PCI. This endeavor may help identify the optimal periprocedural anticoagulation regimen for patient groups with different relative risks of adverse ischemic versus bleeding events, including those with ST-segment and non-ST-segment elevation MI, radial versus femoral access, use of a prolonged bivalirudin infusion or glycoprotein inhibitors, and others. Adherence to standardized techniques and rigorous validation processes should increase confidence in the accuracy and robustness of the results..
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| 8. |
- Demidova, Marina M., et al.
(författare)
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Early repolarization pattern on ECG recorded before the acute coronary event does not predict ventricular fibrillation during ST-elevation myocardial infarction
- 2020
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Ingår i: Heart Rhythm. - : Elsevier BV. - 1547-5271. ; 17:4, s. 629-636
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Tidskriftsartikel (refereegranskat)abstract
- Background: Generally considered benign, electrocardiographic (ECG) early repolarization (ER) pattern was claimed to be an indicator of increased susceptibility to ventricular arrhythmias during acute ischemia. Objective: The purpose of this study was to assess in a nonselected population whether ER pattern documented before ST-elevation myocardial infarction (STEMI) is associated with risk of hemodynamically unstable ventricular tachycardia (VT) or ventricular fibrillation (VF) during acute STEMI. Methods: For STEMI patients admitted for primary percutaneous coronary intervention from 2007–2010, the latest ECGs recorded before STEMI were exported in digital format. After excluding ECGs with paced rhythm and QRS duration ≥120 ms, the remaining ECGs were processed using the Glasgow algorithm allowing automatic ER detection. The association between ER pattern and VT/VF during the first 48 hours of STEMI was tested using logistic regression. Results: ECGs recorded before STEMI were available for 1584 patients. Of these patients, 124 did not meet inclusion criteria, leaving 1460 patients available for analysis (age 68 ± 12 years; 67% male). ER pattern was present in 272 patients (18.6%; ER+ group). ER+ and ER– groups did not differ with regard to clinical characteristics. VT/VF during the first 48 hours of STEMI occurred in 19 ER+ (7.0%) and 105 ER– patients (8.8%; P =.398). ER was not associated with any VT/VF (odds ratio [OR] 0.78; 95% confidence interval [CI] 0.47–1.29; P =.324); VT/VF before reperfusion (OR 0.48; 95% CI 0.23–1.001; P =.051); or reperfusion-related VT/VF (OR 1.28; 95% CI 0.55–3.01; P =.569). Conclusion: In a nonselected population of STEMI patients, the ER pattern on ECG recorded before the acute coronary event was not associated with VT/VF during the first 48 hours of STEMI.
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| 9. |
- Dworeck, Christian, et al.
(författare)
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Radial artery access is associated with lower mortality in patients undergoing primary PCI : a report from the SWEDEHEART registry
- 2020
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Ingår i: European Heart Journal. - : Sage Publications. - 2048-8726 .- 2048-8734. ; 9:4, s. 323-332
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: The purpose of this observational study was to evaluate the effects of radial artery access versus femoral artery access on the risk of 30-day mortality, inhospital bleeding and cardiogenic shock in patients with ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention.Methods: We used data from the SWEDEHEART registry and included all patients who were treated with primary percutaneous coronary intervention in Sweden between 2005 and 2016. We compared patients who had percutaneous coronary intervention by radial access versus femoral access with regard to the primary endpoint of all-cause death within 30 days, using a multilevel propensity score adjusted logistic regression which included hospital as a random effect.Results: During the study period, 44,804 patients underwent primary percutaneous coronary intervention of whom 24,299 (54.2%) had radial access and 20,505 (45.8%) femoral access. There were 2487 (5.5%) deaths within 30 days, of which 920 (3.8%) occurred in the radial access and 1567 (7.6%) in the femoral access group. After propensity score adjustment, radial access was associated with a lower risk of death (adjusted odds ratio (OR) 0.70, 95% confidence interval (CI) 0.55-0.88,P = 0.025). We found no interaction between access site and age, gender and cardiogenic shock regarding 30-day mortality. Radial access was also associated with a lower adjusted risk of bleeding (adjusted OR 0.45, 95% CI 0.25-0.79,P = 0.006) and cardiogenic shock (adjusted OR 0.41, 95% CI 0.24-0.73,P = 0.002).Conclusions: In patients with ST-elevation myocardial infarction, primary percutaneous coronary intervention by radial access rather than femoral access was associated with an adjusted lower risk of death, bleeding and cardiogenic shock. Our findings are consistent with, and add external validity to, recent randomised trials.
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| 10. |
- Gidlöf, Olof, et al.
(författare)
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Inhibition of the long non-coding RNA NEAT1 protects cardiomyocytes from hypoxia in vitro via decreased pri-miRNA processing
- 2020
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Ingår i: Cell Death and Disease. - : Springer Science and Business Media LLC. - 2041-4889. ; 11:8
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Tidskriftsartikel (refereegranskat)abstract
- While restoration of coronary blood flow to the ischemic heart is the most effective strategy for reducing infarct size, reperfusion injury represents a significant limiting factor on clinical outcomes in myocardial infarction patients. Ischemic preconditioning (IPC) has been shown to inhibit reperfusion injury and represents an attractive model for studying cardioprotective signal transduction pathways. Long non-coding RNAs (lncRNAs) are a structurally and functionally heterogenous class of RNA transcripts with unknown roles in IPC-induced cardioprotection. Through microarray-based expression profiling of 31,423 lncRNAs in cardiac tissue from IPC mice, we identified the nuclear transcript Neat1 to be rapidly and robustly decreased in response to IPC. siRNA-mediated knock down of Neat1 reduced apoptosis and necrosis in murine cardiomyocytes (CM) and human iPS-derived CMs in response to prolonged hypoxia and hypoxia-reoxygenation, assessed with Annexin V/propidium iodide-staining, a Caspase 3/7 activity assay, LDH release, and western blot for cleaved Caspase 3. Mechanistically, Neat1 was shown to regulate processing of pro-apoptotic microRNA-22 (miR-22) in murine and human CM nuclei using a luciferase reporter assay. Hypoxia-induced downregulation of Neat1 was shown to result in accumulation of unprocessed pri-miRNA and decreased availability of biologically active miRNA, including miR-22. Addition of exogenous synthetic miR-22 reversed the protective effect of Neat1 knock down in human iPS-CM. In conclusion, we have identified the nuclear lncRNA Neat1 as part of a conserved oxygen-sensitive feedback mechanism by regulation of miRNA processing and a potential target in cardioprotection.
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